Cna-B DOMAIN ANTIGENS IN VACCINES AGAINST GRAM POSITIVE BACTERIA

ABSTRACT

The invention provides protective antigens which are useful in vaccine compositions to induce protection against gram positive bacteria, particularly against  S. agalactiae, S. pyogenes, S. pneumoniae, S. aureus, S. suis , and  S. equi.

This application is a division of Ser. No. 13/144,149, is a nationalphase application of PCT/IB/2010/050110 filed on Jan. 12, 2010, on whichclaims the benefit of U.S. 61/143,859, filed on 12 Jan. 2009. Thecomplete contents of these applications are incorporated herein byreference.

This application incorporates by reference a 335 kb text file created onOct. 11, 2011 and named “PAT052711substitutesequencelisting.txt,” whichis the sequence listing for this application.

FIELD OF THE INVENTION

This invention is in the fields of immunology and vaccinology. Inparticular, it relates to antigens derived from gram positive bacteriaand their use in immunization.

BACKGROUND OF THE INVENTION

Gram positive bacteria include some of the most virulent human andanimal pathogens and are responsible for a long list of severe diseasesand subsequent sequelae. There is a continuing need in the art foreffective vaccines against gram positive bacterial infections.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1A. Amino acid sequence (SEQ ID NO:1) of the Cna_B domain of S.pyogenes protein Cpa_M18 (Spy_M18_(—)0126) cloned together with aflanking domain (“Fb signal”) (“Cna_B-Fb”). FIG. 1B. Graphicrepresentation of cloned domains. See Example 1.

FIG. 2. SDS-polyacrylamide gel containing purified recombinantHis-tagged Cna_B-Fb domain. See Example 1.

FIGS. 3A-D. Western blots demonstrating that the S. pyogenes Cpa_M18(Spy_M18_(—)0126) Cna_B-Fb domain is immunogenic and that Cna_B-Fbdomain antiserum recognizes Cpa and F2 (MGAS2096_SpyO119) proteins fromvarious M strains of S. pyogenes (FIG. 3A, FIG. 3B, FIG. 3C) as well aspili components of S. agalactiae and S. pneumoniae (FIG. 3D). SeeExample 1.

FIGS. 4A-B. Western blots comparing reactivity of Cna_B-Fb antiserum(FIG. 4A) with Cpa_M18 antiserum (FIG. 4B). See Example 1.

FIG. 5. Graph showing results of opsonophagocytosis assays for S.agalactiae strains 515 and JM using antiserum raised against recombinantCna_B-Fb (see Example 1) and differentiated HL-60 cells. See Example 2.

FIG. 6. Graph showing results of opsonophagocytosis assays for S.agalactiae mutant strain R13 (which lacks pili island 2) and itscomplemented strains containing S. pyogenes pilus M1 or S. pyogenespilus M6. See Example 2.

FIG. 7. Alignment of amino acid sequences of Cna_B domains of Cpaproteins from various S. pyogenes strains. Cna_B_Cpa_M5_Manfredo(Spy_M5_(—)0104; SEQ ID NO:18), SEQ ID NO:2; Cna_B_Cpa_M28 (M28_SpyO107,SEQ ID NO:19), SEQ ID NO:3; Cna_B_Cpa_M12 (MGAS2096_Spy0113, SEQ IDNO:20), SEQ ID NO:4; Cna_B_Cpa_M1 (M5005_Spy_(—)0107, SEQ ID NO:21), SEQID NO:5; Cna_B_Cpa_M3 (SpyM3_(—)0098, SEQ ID NO:22), SEQ ID NO:6;Cna_B_Cpa_M18 (spyM18_(—)0126, SEQ ID NO:23), SEQ ID NO:7; Cna_B_Cpa_M6(M6_Spy0159, SEQ ID NO:24), SEQ ID NO:8; Cna_B_Cpa_M4_C(MGAS10750_Spy0115, SEQ ID NO:25), SEQ ID NO:9; Cna_B_Cpa_M2(MGAS10270_Spy0113, SEQ ID NO:26), SEQ ID NO:10.

FIG. 8. Alignment of amino acid sequences of Cna_B domains of piliproteins from S. agalactiae. Cna_B_GBS_(—)52 (SAG_(—)0646, SEQ IDNO:45), SEQ ID NO:27; Cna_B_GBS_(—)150 (SAL 1482, SEQ ID NO:26), SEQ IDNO:28; Cna_B_GBS_(—)104_(—)1 (SAG 0649, SEQ ID NO:47), SEQ ID NO:29;Cna_B_GBS_(—)67 (SAL 1487, SEQ ID NO:48), SEQ ID NO:30;Cna_B_GBS_(—)1523 (SAN 1518, SEQ ID NO:49), SEQ ID NO:31;Cna_B_GBS_(—)1524 (SAN 1519, SEQ ID NO:50), SEQ ID NO:32;Cna_B_GBS_(—)80 (SAG 0645, SEQ ID NO:51), SEQ ID NO:33;Cna_B_GBS_(—)104_(—)2 (SAG 0649, SEQ ID NO:47), SEQ ID NO:34; andCna_B_GBS_(—)1521 (SAN 1516, SEQ ID NO:52), SEQ ID NO:35.

FIG. 9. Alignment of amino acid sequences of GBS island 1 pilicomponents with a Cna_B domain of S. pyogenes Cpa protein from strainM18. Cna_B_GBS_(—)80 (SAG 0645, SEQ ID NO:51), SEQ ID NO:33;Cna_B_GBS_(—)52 (SAG 0646, SEQ ID NO:45), SEQ ID NO:27;Cna_B_GBS_(—)104_(—)2 (SAG 0649, SEQ ID NO:47), SEQ ID NO:34;Cna_B_GBS_(—)104_(—)1 (SAG 0649, SEQ ID NO:47), SEQ ID NO:29; andCna_B_CPA_M18 (Spy_M18_(—)0126, SEQ ID NO:23), SEQ ID NO:7.

FIG. 10. Alignment of amino acid sequences of GBS island 2 pilicomponents with a Cna_B domain of S. pyogenes Cpa protein from strainM18. Cna_B_CPA_M18 (Spy_M18_(—)0126, SEQ ID NO:23), SEQ ID NO:7;Cna_B_GBS_(—)150 (SAL 1482, SEQ ID NO:46), SEQ ID NO:28; Cna_B_GBS_(—)67(SAL 1487, SEQ ID NO:48), SEQ ID NO:30; and Cna_B_GBS_(—)59 (SAL 1486,SEQ ID NO:102), SEQ ID NO:103.

FIG. 11. Alignment of amino acid sequences of GBS island 3 pilicomponents with a Cna_B domain of S. pyogenes Cpa protein from strainM18. Cna_B_CPA_M18 (Spy_M18_(—)0126, SEQ ID NO:23), SEQ ID NO:7;Cna_B_GBS_(—)1524 (SAN 1519, SEQ ID NO:50), SEQ ID NO:32; andCna_B_GBS_(—)1523 (SAN 1518, SEQ ID NO:49), SEQ ID NO:31.

FIG. 12. Alignment of amino acid sequences of S. pneumoniae pili strainTIGR4 components with a Cna_B domain of S. pyogenes Cpa protein fromstrain M18. Cna_B_CPA_M18 (Spy_M18_(—)0126, SEQ ID NO:23), SEQ ID NO:7;RrgB (SP_(—)0463, SEQ ID NO:63), SEQ ID NO:53; RrgA1 (SP_(—)0462, SEQ IDNO:64), SEQ ID NO:54; RrgC2 (SP_(—)0464, SEQ ID NO:65), SEQ ID NO:56;RrgA2 (SP_(—)0462, SEQ ID NO:64), SEQ ID NO:57; and RrgC1 (SP_(—)0464,SEQ ID NO:65), SEQ ID NO:58.

FIG. 13. Alignment of amino acid sequences of S. aureus proteinscomprising a Cna_B domain with a Cna_B domain of S. pyogenes Cpa proteinfrom strain M18. Ser-Asp rich2 (SdrD MW0517, SEQ ID NO:72), SEQ IDNO:66; Ser-Asp rich3 (SdrD MW0517, SEQ ID NO:72), SEQ ID NO:67; CBP(MW2612, SEQ ID NO:73), SEQ ID NO:68; and Cna_B_CPA_M18(Spy_M18_(—)0126, SEQ ID NO:23), SEQ ID NO:7.

FIG. 14A. Western blot demonstrating that Cna_B antiserum recognized S.suis recombinant proteins. FIG. 14B, amino acid sequences ofCna_B_CPA_M18 (Spy_M18_(—)0126, SEQ ID NO:23), SEQ ID NO:14; Cna_B_Bkb3(DUF 11) 89/1591 (SEQ ID NO:83), SEQ ID NO:75: Cna_B Bbk1 SSU05 047405AYH33 (SEQ ID NO:82), SEQ ID NO:76.

FIG. 15A. Western blot demonstrating that Cna_B antiserum recognizes S.equi recombinant proteins. FIG. 15B, amino acid sequences ofCna_B_CPA_M18 (Spy_M18_(—)0126, SEQ ID NO:23), SEQ ID NO:14; BKB SEQ0936(SEQ ID NO:88), SEQ ID NO:77; ancillary protein SEQ 0935 (SEQ ID NO:87),SEQ ID NO:78.

FIG. 16. Alignment of Cna_B domains of S. pyogenes Cpa protein(Spy_M18_(—)0126, SEQ ID NO:23) (SEQ ID NO:7) with Cna_B domains of twoS. suis proteins. Cna_B_AUTOTRANSPORTER (SEQ ID NO:82), SEQ ID NO:80;Cna_B_(SEQ ID NO:83), SEQ ID NO:81.

FIG. 17. Alignment of Cna_B domains of S. pyogenes Cpa protein(Spy_M18_(—)0126, SEQ ID NO:23) (SEQ ID NO:7) with Cna_B domains of twoS. equi proteins. Cna_B_bkb (SEQ ID NO:88), SEQ ID NO:86; Cna_B_ap1 (SEQID NO:87), SEQ ID NO:84; Cna_B_ap2 (SEQ ID NO:87), SEQ ID NO:85.

FIG. 18A. FACS analysis of GAS Cna_B serum cross-reaction with selectedGBS strains. FIG. 18B. FACS analysis of GAS Cna_B serum cross-reactionwith selected GBS strains.

FIG. 19. Graph showing results of ELISA assays described in Example 4.

FIG. 20. Western blots demonstrating that antiserum against a Cna_Bdomain antigen recognizes GBS pili in a GBS protein extraction.“α-GAS_Cna_B_M18” is antiserum from mice immunized with Cna_B-Fb-M18, asdescribed in Example 1.

FIG. 21. Graph demonstrating that mice immunized with a Cna_B domainantigen show reduced skin lesion area in a GAS subcutaneous infectionmodel. See Example 6.

FIG. 22. Graph demonstrating that mice immunized with a Cna_B domainantigen show a reduced nasopharyngeal colonization rate when challengedwith S. aureus. See Example 7.

FIG. 23A. Graph demonstrating that mice immunized with a Cna_B domainantigen show reduced nasopharyngeal colonization rates when challengedwith S. aureus. FIG. 23B. Graph demonstrating that mice immunized with aCna_B domain antigen show reduced nasopharyngeal colonization rates whenchallenged with S. aureus. See Example 9.

FIG. 24. Graphs demonstrating that mice born from mothers immunized witha chimeric Cna_B domain antigen show an increased survival rate overcontrols when immunized with a chimeric Cna_B domain antigen. SeeExample 1.

FIG. 25. Graph demonstrating that immunized with a chimeric Cna_B domainantigen show reduced skin lesion area in a GAS subcutaneous infectionmodel. See Example 6.

FIGS. 26A-B. Graphic representation and amino acid sequence (SEQ IDNO:132) of the SdrD protein of S. aureus subsp. aureus NCTC 8325 (FIG.26A); graphic representation of the same Cna_B domain antigen and itsamino acid sequence (SEQ ID NO:132), indicating the Cna_B domains (FIG.26B).

FIGS. 27A-C. Cloning, expression, and purification of Cna_B domains.FIG. 27A, Graphic representation of cloned Cna_B domains (SEQ IDNOS:134-138) of SdrD. FIG. 27B, amino acid sequence of the cloneddomains (SEQ ID NO:133). FIG. 27C, SDS-polyacrylamide gel containing thepurified Cna_B domains.

FIG. 28. Graph demonstrating that Cna_B_SdrD confers protection in amouse model against infection with S. aureus strain USA300.

DETAILED DESCRIPTION OF THE INVENTION

A “Cna_B domain” was first described in an S. aureus collagen-bindingsurface protein as a region that does not mediate collagen binding. Thestructure of the repetitive B-region forms a beta sandwich structure. Itis thought that this region forms a stalk in the S. aureuscollagen-binding protein that presents the ligand binding domain awayfrom the bacterial cell surface. Proteins containing a Cna_B domain arepresent in a variety of Gram positive pathogenic bacteria, including S.aureus, S. pneumoniae, S. agalactiae (GBS), S. pyogenes (GAS), S. equi,S. suis, C. perifringens, L. monocytogenes, B. thuringiensis, P.acidigallici, E. faceium, B. cereus, S. epidermidis, E. faecalis, C.difficile, C. diphtheriae, S. gordonii, S. dysgalactiae, and C. tetani.

As described in the specific examples, below, the Cna_B domain (SEQ IDNO:7) of S. pyogenes Cpa protein (Spy_M18_(—)0126, SEQ ID NO:23) isimmunogenic. Specific antibodies raised against it recognize recombinantproteins of S. pyogenes, S. agalactiae, S. pneumoniae, S. suis, and S.equi. About half of the antibodies contained in GAS_Cpa_M18 proteinserum are specific for the Cna_B domain, and antiserum raised againstthe Cna_B domain of S. pyogenes Cpa protein from strain M18 (“anti-Cna_Bserum”) detects in a Western blot proteins which were not detected withantiserum raised against the entire protein (“GAS_M18_cpa”) and mediatesthe phagocytic killing of S. agalactiae. The Cna_B domain ofSpy_M18_(—)0126 also mediates passive protection in GBS-challenged mice.Thus, there is an advantage to raising antibodies against streptococcalCna_B domains or Cna_B domains of other gram positive bacterial proteins(e.g., S. aureus).

The invention provides Cna_B domain antigens which are useful in vaccinecompositions to induce protection against gram positive bacteria,particularly against one or more of S. aureus, S. pneumoniae, S.agalactiae (GBS), S. pyogenes (GAS), S. equi, and S. suis. The inventionalso provides methods of using Cna_B domain antigens to induceantibodies and to treat or protect against gram positive bacterialinfections, including cross-protection between various streptococcaland/or staphylococcal species.

Cna_B Domains

Cna_B domains from any gram positive bacterial protein can be used incompositions and methods of the invention. Amino acid sequences of Cna_Bdomains from various S. aureus, S. pneumoniae, S. agalactiae, S.pyogenes, S. suis, and S. equis proteins are shown in FIGS. 7-13, 16,and 17 and set forth in the sequence listing as SEQ ID NOS:2-10, 27-35,53-57, 66, 67, 75, 76, 80, 81, 84-86, 110-117, 122-126, and 134-138.Examples of other proteins containing Cna_B domains are shown in SEQ IDNOS:89-102 and 132. The Cna_B domains typically contain one or moresequences identified in FIGS. 7-13 as a “G box.” A consensus sequenceamino acid sequence for the G boxes shown in FIGS. 7-13 is shown in SEQID NO:74.

Variants

In some embodiments, variants of Cna_B domains of the invention haveamino acid sequences which are at least 90% identical, at least 95%identical, at least 96% identical, at least 97% identical, at least 98%identical, or at least 99% identical to any of SEQ ID NOS:2-10, 27-35,53-57, 66, 67, 75, 76, 80, 81, 84-86, 110-117, 122-126, and 134-138.Typically any difference between the amino acid sequence of a Cna_Bdomain and the amino acid sequence of a variant of the Cna_B domain isdue to one or more conservative amino acid substitutions (typically 1,2, 3, 4, 5, 6, 7, or 8 substitutions). However, amino acid deletions orinsertions also are possible.

In some embodiments conservative amino acid substitutions are based onchemical properties and include substitution of a positively-chargedamino acid for another positively charged amino acid (e.g., H, K, R); anegatively-charged amino acid for another negatively charged amino acid(e.g., D, E); a very hydrophobic amino acid for another very hydrophobicamino acid (e.g., C, F, I, L, M, V, W); a less hydrophobic amino acidfor another less hydrophobic amino acid (e.g., A, G, H, P, S, T, Y); apartly hydrophobic amino acid for another partly hydrophobic amino acid(e.g., K, R); an aliphatic amino acid for another aliphatic amino acid(e.g., A, I, L, M, P, V); a polar amino acid for another polar aminoacid (e.g., A, D, E, G, H, K, N, P, Q, R, S, T, Y); an aromatic aminoacid for another aromatic amino acid (e.g., F, H, W, Y); and a smallamino acid for another small amino acid (e.g., D, N, T).

In some embodiments, conservative amino acid substitutions aredetermined using the BLOSUM62 table. The BLOSUM62 table is an amino acidsubstitution matrix derived from about 2,000 local multiple alignmentsof protein sequence segments, representing highly conserved regions ofmore than 500 groups of related proteins (Henikoff & Henikoff, Proc.Natl. Acad. Sci. USA 89:10915, 1992). The BLOSUM62 substitutionfrequencies can be used to define conservative amino acid substitutionsthat may be introduced into amino acid sequences of Cna_B domains. Inthese embodiments a conservative substitution preferably refers to asubstitution represented by a BLOSUM62 value of greater than −1. Forexample, an amino acid substitution is conservative if the substitutionis characterized by a BLOSUM62 value of 0, 1, 2, or 3. According to thissystem, preferred conservative amino acid substitutions arecharacterized by a BLOSUM62 value of at least 1 (e.g., 1, 2, or 3),while more preferred conservative amino acid substitutions arecharacterized by a BLOSUM62 value of at least 2 (e.g., 2 or 3).

Particular amino acid substitutions or alterations can be identified byaligning the Cna_B domains as shown in FIGS. 7-13. Cna_B domain antigens(described below) including any combination of such options is withinthe scope of the invention.

Cna_B Domain Antigens

“Cna_B domain antigens” comprise one or more Cna_B domains as describedabove and may or may not comprise additional amino acids at the Nterminus, C terminus, or both. In some embodiments, Cna_B domainantigens consist of any of SEQ ID NOS:1-10, 27-35, 53-57, 66-68, 75, 76,80, 81, 84-86, 110-117, 122-126, and 133-138. In other embodiments,Cna_B domain antigens comprise a Cna_B domain as well as other aminoacid sequences which are not directly adjacent to a Cna_B domain in anative bacterial (e.g., streptococcal or staphylococcal) protein. Thatis, in such antigens the amino group of the N terminal amino acid of aCna_B domain is not linked by a peptide bond to the carboxyl group of anamino acid to which it is linked in a native bacterial (e.g.,streptococcal or staphylococcal) protein and/or the carboxyl group ofthe C terminal amino acid of the Cna_B domain is not linked by a peptidebond to the amino group of an amino acid to which it is linked in anative gram positive bacterial protein, e.g., a protein of S. aureus, S.pneumoniae, S. agalactiae (GBS), S. pyogenes (GAS), S. equi, or S. suis.“Native” gram positive bacterial proteins are proteins which are foundin gram positive bacterial as they exist in nature; “native”streptococcal or staphylococcal proteins are proteins which are found instreptococcal or staphylococcal bacteria, respectively, as they exist innature.

In still other embodiments, Cna_B domain antigens consist of a Cna_Bdomain as well as additional amino acids at the N and/or C terminal(s)of the domain, provided that the Cna_B domain antigen does not consistof a full-length bacterial (e.g., streptococcal or staphylococcal)protein (see Tables 1-32).

In other embodiments, Cna_B domain antigens consist of polypeptides ofthe formula:

A(LB)_(n)

wherein A is a first Cna_B domain; B is a second Cna_B domain; n is aninteger (typically 1-10; e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10); and Lis independently absent or is an amino acid linker. The Cna_B domains insuch antigens can be the same, different, or a mixture of some Cna_Bdomains which are the same and some which are different (i.e., all theCna_B domains can be different or two or more of the Cna_B domains canbe the same). For example, the Cna_B domains can be domains of two ormore different gram positive proteins, particularly proteins of grampositive cocci, such as streptococcal proteins, staphylococcal proteins,or of proteins of two or more different species or strains (e.g., S.agalactiae, S. pyogenes, S. pneumoniae, S. aureus, S. suis, and/or S.equi).

The amino acid linker, if present between any of the Cna_B domains,typically contains between 6 and 12 amino acids (e.g., 6, 7, 8, 9, 10,11, or 12). GSGGGG (SEQ ID NO:79) is an example of a useful linker.Linkers in a Cna_B domain antigen can be the same or different.

Examples of Cna_B domain antigens of formula A(LB)_(n) include proteinscomprising or consisting of SEQ ID NO:108. SEQ ID NO:108 comprises, fromN to C terminus, a Cna_B domain of SAG 0645 (SEQ ID NO:112), the aminoacid sequence VDS, a first amino acid linker (SEQ ID NO:79), a Cna_Bdomain of SAN_(—)1518 (SEQ ID NO:113), a second amino acid linker (SEQID NO:79), a first Cna_B domain of SAL_(—)1487 (SEQ ID NO:110), theamino acid sequence NSG, a second Cna_B domain of SAL_(—)1487 (SEQ IDNO:111), and the amino acid KQI.

Other examples of Cna_B domain antigens of formula A(LB)_(n) includeproteins comprising or consisting of SEQ ID NO:109. SEQ ID NO:109comprises, from N to C terminus, Cna_B domain of SAG_(—)0645 (SEQ IDNO:112), the amino acid sequence VDS, a first amino acid linker (SEQ IDNO:79), a Cna_B domain of SAN_(—)1518 (SEQ ID NO:113), a second aminoacid linker (SEQ ID NO:79), a first Cna_B domain of SAL_(—)1486 (114),the amino acid sequence LPL, a second Cna_B domain of SAL_(—)1486 (SEQID NO:115), and the amino acid sequence DIE.

Other examples of Cna_B domain antigens of formula A(LB)_(n) includeproteins which comprise or consist of SEQ ID NOS:127, 128, 129, 130,131, 133, 134, 135, 136, 137, or 138; see Examples 8 and 10.

In the Cna_B domain antigens described above, the amino acid sequencesVDS, NSG, KQI, LPL, and DIE are included so as not to truncate a betapleated sheet. It is well within the skill of the ordinary artisan toinclude other such amino acid sequences in Cna_B domain antigens of theinvention to help preserve tertiary structure of Cna_B domains.

Still other examples of Cna_B domain antigens of formula A(LB)_(n)comprise:

-   -   a. Cna_B domains of S. pyogenes Spy_M18_(—)0126 (e.g., SEQ ID        NO:7) and M6_Spy0159) (e.g., SEQ ID NO:8), and MGAS2096_Spy0119        (e.g., SEQ ID NO:121); these include Cna_B domain antigens which        comprise fusions of the five Cna_B domains (SEQ ID NOS:122-126)        of SEQ ID NO:121. A coding sequence for the Cna_B domain of        Spy0159 is shown in SEQ ID NO:120. A coding sequence for Spy0119        is shown in SEQ ID NO:119. Nucleotides 181-390, 1576-1797,        1915-2127, 2281-2496, and 2716-2916 of SEQ ID NO:121 encode the        Cna_B domains shown in SEQ ID NOS:122-126, respectively.    -   b. Cna_B domains of S. aureus SdrD (e.g., SEQ ID NOS:134-138;        SEQ ID NO:66 and/or 67; SEQ ID NO:139) and Cna_B cap (e.g., SEQ        ID NO:68).    -   c. Cna_B domains of S. pneumoniae SP_(—)0463) (e.g., SEQ ID        NO:53), Cna_B_RrgA (SP_(—)0462) (e.g., SEQ ID NO:54 and/or 56),        and Cna_B RrgC (SP_(—)0464) (e.g., SEQ ID NO:55 and/or 57).    -   d. Cna_B domains of Spy_M18_(—)0126 (e.g., SEQ ID NO:7), SAG        0645 (SEQ ID NO:33), RrgB (SP_(—)0463) (e.g., SEQ ID NO:53), and        SdrD (e.g., SEQ ID NOS:134-138; SEQ ID NO:66 and/or 67; SEQ ID        NO:139).

Cna_B domain antigens of the invention also can comprise any of theCna_B domain antigens described above. In some of these embodiments, theamino group of the N terminal amino acid of the Cna_B domain is notlinked by a peptide bond to the carboxyl group of an amino acid to whichit is linked in a native bacterial (e.g., streptococcal orstaphylococcal) protein and/or the carboxyl group of the C terminalamino acid of the Cna_B domain is not linked by a peptide bond to theamino group of an amino acid to which it is linked in a native bacterial(e.g., streptococcal or staphylococcal) protein.

In some embodiments, one or more Cna_B domain antigens of the inventionare part of a fusion polypeptide which comprises another bacterialantigen, preferably another bacterial (e.g., streptococcal orstaphylococcal) antigen. Suitable antigens are disclosed, e.g., in WO99/05447, WO 02/034771, WO 04/018646, WO 05/028618, WO 05/032482, WO06/042027, and WO 06/078318.

Fusion polypeptides comprising one or more Cna_B domains and otherdomains, such as von Willenbrand Factor A (vWFA) domains (e.g., SEQ IDNOS:105, 106, 107), are also within the scope of the invention, such as:

a. a Cna_B domain of Spy_M18_(—)0126) (e.g., SEQ ID NO:7) andvWFA_cpa_M6 (M6_Spy0159) (e.g., SEQ ID NO:105); and

-   -   b. a Cna_B domain of SAG 0645 (e.g., SEQ ID NO:33) and        vWFA_SAL_(—)1487 (e.g., SEQ ID NO:106).

Such fusion polypeptides can include linker sequences between thevarious fusion partners and/or flanking sequences from each of thefusion partners, which can be selected from those disclosed in Tables1-37 and 43-48, below.

TABLE 1 Cna_B domain antigens comprising SEQ ID NO: 2 (Spy_M5_0104, SEQID NO: 18; >gi|139472985|ref|YP_001127700.1| putative surface-anchoredprotein [Streptococcus pyogenes str. Manfredo]) number of additionalcontiguous amino acids of SEQ ID NO: 18 at N terminus of SEQ ID NO: 2number of additional contiguous amino acids of SEQ ID NO: 18 at Cterminus of SEQ ID NO: 2 0-70, e.g., 0, 1, 2, 3, 4, 5, 0-390, e.g., 0,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 6, 7, 8, 9, 10, 11, 12,13, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49,50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 14, 15,16, 17, 18, 19, 20, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78,79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96,97, 98, 21, 22, 23, 24, 25, 26, 27, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119,120, 121, 122, 123, 28, 29, 30, 31, 32, 33, 34, 124, 125, 126, 127, 128,129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142,143, 144, 145, 146, 147, 148, 35, 36, 37, 38, 39, 40, 41, 149, 150, 151,152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165,166, 167, 168, 169, 170, 171, 172, 173, 42, 43, 44, 45, 46, 47, 48, 174,175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188,189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 49, 50, 51, 52, 53,54, 55, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211,212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 56, 57, 58,59, 60, 61, 62, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234,235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248,63, 64, 65, 66, 67, 68, 69, 249, 250, 251, 252, 253, 254, 255, 256, 257,258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271,272, 273, 70 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285,286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299,300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313,314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327,328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341,342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355,356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369,370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383,384, 385, 386, 387, 388, 389, 390

TABLE 2 Cna_B domain antigens comprising SEQ ID NO: 3 (M28_Spy0107, SEQID NO: 19; >gi|71902773|ref|YP_279576.1| collagen-binding protein[Streptococcus pyogenes MGAS6180]) number of additional contiguous aminoacids of number of additional contiguous amino acids of SEQ ID NO: 19 atC SEQ ID NO: 19 at N terminus of SEQ ID NO: 3 terminus of SEQ ID NO: 30-294, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 0-390, e.g., 0,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,21, 22, 23, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 48,49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66,67, 68, 69, 70, 71, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63,64, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109,110, 111, 112, 113, 114, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76,77, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127,128, 129, 130, 131, 132, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145,146, 147, 148, 149, 150, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101,102, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163,164, 165, 166, 167, 168, 103, 104, 105, 106, 107, 108, 109, 110, 111,169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186, 112, 113, 114, 115, 116, 117, 118, 119, 120, 187,188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201,202, 203, 204, 121, 122, 123, 124, 125, 126, 127, 128, 129, 205, 206,207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220,221, 222, 130, 131, 132, 133, 134, 135, 136, 137, 138, 223, 224, 225,226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239,240, 139, 140, 141, 142, 143, 144, 145, 146, 147, 241, 242, 243, 244,245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258,148, 149, 150, 151, 152, 153, 154, 155, 156, 259, 260, 261, 262, 263,264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 157,158, 159, 160, 161, 162, 163, 164, 165, 277, 278, 279, 280, 281, 282,283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 166, 167,168, 169, 170, 171, 172, 173, 174, 295, 296, 297, 298, 299, 300, 301,302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 175, 176, 177,178, 179, 180, 181, 182, 183, 313, 314, 315, 316, 317, 318, 319, 320,321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 184, 185, 186, 187,188, 189, 190, 191, 192, 331, 332, 333, 334, 335, 336, 337, 338, 339,340, 341, 342, 343, 344, 345, 346, 347, 348, 193, 194, 195, 196, 197,198, 199, 200, 201, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358,359, 360, 361, 362, 363, 364, 365, 366, 202, 203, 204, 205, 206, 207,208, 209, 210, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377,378, 379, 380, 381, 382, 383, 384, 211, 212, 213, 214, 215, 216, 217,218, 219, 385, 386, 387, 388, 389, 390 220, 221, 222, 223, 224, 225,226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239,240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253,254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267,268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281,282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294

TABLE 3 Cna_B domain antigens comprising SEQ ID NO: 4 (MGAS2096_Spy0113,SEQ ID NO: 20; >gi|94991610|ref|YP_599709.1| fibronectin-binding protein[Streptococcus pyogenes MGAS2096]) number of additional contiguous aminoacids of SEQ ID number of additional contiguous amino acids of SEQ IDNO: 20 at C NO: 20 at N terminus of SEQ ID NO: 4 terminus of SEQ ID NO:4 0-297, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,0-396, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,27, 28, 29, 30, 31, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36,37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 32, 33, 34, 35, 36, 37, 38,39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56,57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 48, 49, 50,51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 72, 73, 74, 75, 76,77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94,95, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 96,97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111,112, 113, 114, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93,94, 95, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127,128, 129, 130, 131, 132, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143,144, 145, 146, 147, 148, 149, 150, 109, 110, 111, 112, 113, 114, 115,116, 117, 118, 119, 120, 151, 152, 153, 154, 155, 156, 157, 158, 159,160, 161, 162, 163, 164, 165, 166, 167, 168, 121, 122, 123, 124, 125,126, 127, 128, 129, 130, 131, 132, 169, 170, 171, 172, 173, 174, 175,176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 133, 134, 135,136, 137, 138, 139, 140, 141, 142, 143, 144, 187, 188, 189, 190, 191,192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 145,146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 205, 206, 207,208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221,222, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 223,224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237,238, 239, 240, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179,180, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253,254, 255, 256, 257, 258, 181, 182, 183, 184, 185, 186, 187, 188, 189,190, 191, 192, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 193, 194, 195, 196, 197, 198, 199,200, 201, 202, 203, 204, 277, 278, 279, 280, 281, 282, 283, 284, 285,286, 287, 288, 289, 290, 291, 292, 293, 294, 205, 206, 207, 208, 209,210, 211, 212, 213, 214, 215, 216, 295, 296, 297, 298, 299, 300, 301,302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 217, 218, 219,220, 221, 222, 223, 224, 225, 226, 227, 228, 313, 314, 315, 316, 317,318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 229,230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 331, 332, 333,334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347,348, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 349,350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363,364, 365, 366, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263,264, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379,380, 381, 382, 383, 384, 265, 266, 267, 268, 269, 270, 271, 272, 273,274, 275, 276, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395,396 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289,290, 291, 292, 293, 294, 295, 296, 297

TABLE 4 Cna_B domain antigens comprising SEQ ID NO: 5 (M5005_Spy_0107,SEQ ID NO: 21; >gi|71909921|ref|YP_281471.1| fibronectin-binding protein[Streptococcus pyogenes MGAS5005]) number of additional contiguous aminoacids of SEQ ID NO: 21 number of additional contiguous amino acids ofSEQ ID NO: 21 at N terminus of SEQ ID NO: 5 at C terminus of SEQ ID NO:5 0-310, e.g., 0, 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11,12, 13, 14, 15, 16,17, 18, 0-380, e.g., 0, 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11,12, 13, 14, 15,16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34,35, 36, 37, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, 35, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,53, 54, 55, 56, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49,50, 51, 52, 53, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70,71, 72, 73, 74, 75, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66,67, 68, 69, 70, 71, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88,89, 90, 91, 92, 93, 94, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104,105, 106, 107, 108, 109, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100,101, 102, 103, 104, 105, 110, 111, 112, 113, 114, 115, 116, 117, 118,119, 120, 121, 122, 123, 106, 107, 108, 109, 110,1 11, 112, 113, 114,115, 116, 117, 118, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133,134, 135, 136, 137, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,129, 130, 131, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148,149, 150, 151, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142,143, 144, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163,164, 165, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156,157, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178,179, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170,180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193,171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 194,195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 184,185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 208, 209,210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 197, 198,199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 222, 223, 224,225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 210, 211, 212,213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 236, 237, 238, 239,240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 223, 224, 225, 226,227, 228, 229, 230, 231, 232, 233, 234, 235, 250, 251, 252, 253, 254,255, 256, 257, 258, 259, 260, 261, 262, 263, 236, 237, 238, 239, 240,241, 242, 243, 244, 245, 246, 247, 248, 264, 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 277, 249, 250, 251, 252, 253, 254,255, 256, 257, 258, 259, 260, 261, 278, 279, 280, 281, 282, 283, 284,285, 286, 287, 288, 289, 290, 291, 262, 263, 264, 265, 266, 267, 268,269, 270, 271, 272, 273, 274, 292, 293, 294, 295, 296, 297, 298, 299,300, 301, 302, 303, 304, 305, 275, 276, 277, 278, 279, 280, 281, 282,283, 284, 285, 286, 287, 306, 307, 308, 309, 310 288, 289, 290, 291,292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305,306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319,320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333,334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347,348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361,362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375,376, 377, 378, 379, 380

TABLE 5 Cna_B domain antigens comprising SEQ ID NO: 6 (SpyM3_0098, SEQID NO: 22; >gi|21909634|ref|NP_663902.1| putative collagen bindingprotein [Streptococcus pyogenes MGAS315]) number of additionalcontiguous amino acids of SEQ ID NO: 22 number of additional contiguousamino acids of SEQ ID NO: 22 at N terminus of SEQ ID NO: 6 at C terminusof SEQ ID NO: 6 0-288, e.g., 0, 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11,12, 13,14, 15, 16, 17, 0-393, e.g., 0, 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,49, 50, 51, 52, 53, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66,67, 68, 69, 70, 71, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66,67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84,85, 86, 87, 88, 89, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84,85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101,102, 103, 104, 105, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101,102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115,116, 117, 118, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116,117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130,131, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131,132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 132,133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146,147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 145, 146, 147,148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161,162, 163, 164, 165, 166, 167, 168, 169, 170, 158, 159, 160, 161, 162,163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176,177, 178, 179, 180, 181, 182, 183, 171, 172, 173, 174, 175, 176, 177,178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191,192, 193, 194, 195, 196, 184, 185, 186, 187, 188, 189, 190, 191, 192,193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206,207, 208, 209, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207,208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221,222, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222,223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 223,224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237,238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 236, 237, 238,239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252,253, 254, 255, 256, 257, 258, 259, 260, 261, 249, 250, 251, 252, 253,254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267,268, 269, 270, 271, 272, 273, 274, 262, 263, 264, 265, 266, 267, 268,269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282,283, 284, 285, 286, 287, 275, 276, 277, 278, 279, 280, 281, 282, 283,284, 285, 286, 287, 288 288, 289, 290, 291, 292, 293, 294, 295, 296,297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310,311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324,325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338,339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352,353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366,367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380,381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393

TABLE 6 Cna_B domain antigens comprising SEQ ID NO: 7 (Spy_M18_0126, SEQID NO: 23; >gi|19745301|ref|NP_606437.1| putative collagen bindingprotein [Streptococcus pyogenes MGAS8232]) number of additionalcontiguous amino acids of SEQ ID NO: 23 at N terminus of SEQ ID NO: 7number of additional contiguous amino acids of SEQ ID NO: 23 at Cterminus of SEQ ID NO: 7 0-70, e.g., 0, 1, 2, 3, 4, 0-392, e.g., 0, 1,2, 3, 4, 5, 6,7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 24, 25, 26, 27, 28, 29, 5, 6, 7, 8, 9, 10, 11, 12, 30, 31, 32,33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50,51, 52, 53, 54, 55, 56, 57, 58, 13, 14, 15, 16, 17, 18, 59, 60, 61, 62,63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80,81, 82, 83, 84, 85, 86, 87, 19, 20, 21, 22, 23, 24, 88, 89, 90, 91, 92,93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108,109, 110, 111, 112, 25, 26, 27, 28, 29, 30, 113, 114, 115, 116, 117,118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131,132, 133, 134, 31, 32, 33, 34, 35, 36, 135, 136, 137, 138, 139, 140,141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154,155, 156, 37, 38, 39, 40, 41, 42, 157, 158, 159, 160, 161, 162, 163,164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177,178, 43, 44, 45, 46, 47, 48, 179, 180, 181, 182, 183, 184, 185, 186,187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200,49, 50, 51, 52, 53, 54, 201, 202, 203, 204, 205, 206, 207, 208, 209,210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 55, 56,57, 58, 59, 60, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233,234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 61, 62, 63, 64,65, 66, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257,258, 259, 260, 261, 262, 263, 264, 265, 266, 67, 68, 69, 70 267, 268,269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282,283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296,297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310,311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324,325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338,339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352,353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366,367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380,381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392

TABLE 7 Cna_B domain antigens comprising SEQ ID NO: 8 (M6_Spy0159, SEQID NO: 24; >gi|50913505|ref|YP_059477.1| collagen adhesion protein[Streptococcus pyogenes MGAS10394]) number of additional contiguousamino acids of number of additional contiguous amino acids of SEQ ID NO:24 SEQ ID NO: 24 at C at N terminus of SEQ ID NO: 8 terminus of SEQ IDNO: 8 0-906, e.g., 0, 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11,12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 0-58, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8,24, 25, 26, 27, 28, 29, 30, 31,32, 33, 34, 35, 36, 37, 38, 39, 40, 41,42, 43, 44, 45, 46, 47, 9, 10, 11, 12, 13, 14, 15, 16, 17, 48, 49, 50,51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64,65, 66, 67, 68,69, 70, 71, 18, 19, 20, 21, 22, 23, 24, 25, 26, 72, 73, 74, 75, 76, 77,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,27, 28, 29, 30, 31, 32, 33, 34, 35, 96, 97, 98, 99, 100, 101, 102, 103,104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 36, 37, 38, 39,40, 41, 42, 43, 44, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124,125, 126, 127, 128, 129, 130, 131, 132, 45, 46, 47, 48, 49, 50, 51, 52,53, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145,146, 147, 148, 149, 150, 54, 55, 56, 57, 58 151, 152, 153, 154, 155,156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169,170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183,184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197,198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211,212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225,226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239,240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253,254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267,268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281,282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295,296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309,310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323,324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337,338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351,352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365,366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379,380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393,394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407,408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421,422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435,436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449,450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463,464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477,478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491,492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505,506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519,520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533,534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547,548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561,562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575,576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589,590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603,604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617,618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631,632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645,646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659,660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673,674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687,688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701,702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715,716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729,730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743,744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757,758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771,772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785,786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799,800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813,814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827,828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841,842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855,856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868, 869,870, 871, 872, 873, 874, 875, 876, 877, 878, 879, 880, 881, 882, 883,884, 885, 886, 887, 888, 889, 890, 891, 892, 893, 894, 895, 896, 897,898, 899, 900, 901, 902, 903, 904, 905, 906

TABLE 8 Cna_B domain antigens comprising SEQ ID NO: 9(MGAS10750_Spy0115, SEQ ID NO: 25; >gi|94993511|ref|YP_601609.1|Fibronectin-binding protein [Streptococcus pyogenes MGAS10750] number ofadditional contiguous amino acids of SEQ ID NO: 25 number of additionalcontiguous amino acids of SEQ ID NO: 25 at N terminus of SEQ ID NO: 9 atC terminus of SEQ ID NO: 9 0-654, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 0-646, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,27, 28, 29, 30, 31, 32, 33, 34, 35, 18, 19, 20, 21, 22, 23, 24, 25, 26,27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44,45, 46, 47, 48, 49, 50, 51, 52, 53, 36, 37, 38, 39, 40, 41, 42, 43, 44,45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62,63, 64, 65, 66, 67, 68, 69, 70, 71, 54, 55, 56, 57, 58, 59, 60, 61, 62,63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80,81, 82, 83, 84, 85, 86, 87, 88, 89, 72, 73, 74, 75, 76, 77, 78, 79, 80,81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98,99, 100, 101, 102, 103, 104, 105, 90, 91, 92, 93, 94, 95, 96, 97, 98,99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112,113, 114, 115, 116, 117, 118, 119, 106, 107, 108, 109, 110, 111, 112,113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126,127, 128, 129, 130, 131, 132, 133, 120, 121, 122, 123, 124, 125, 126,127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140,141, 142, 143, 144, 145, 146, 147, 134, 135, 136, 137, 138, 139, 140,141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154,155, 156, 157, 158, 159, 160, 161, 148, 149, 150, 151, 152, 153, 154,155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168,169, 170, 171, 172, 173, 174, 175, 162, 163, 164, 165, 166, 167, 168,169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186, 187, 188, 189, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196,197, 198, 199, 200, 201, 202, 203, 190, 191, 192, 193, 194, 195, 196,197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210,211, 212, 213, 214, 215, 216, 217, 204, 205, 206, 207, 208, 209, 210,211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224,225, 226, 227, 228, 229, 230, 231, 218, 219, 220, 221, 222, 223, 224,225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238,239, 240, 241, 242, 243, 244, 245, 232, 233, 234, 235, 236, 237, 238,239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252,253, 254, 255, 256, 257, 258, 259, 246, 247, 248, 249, 250, 251, 252,253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266,267, 268, 269, 270, 271, 272, 273, 260, 261, 262, 263, 264, 265, 266,267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294,295, 296, 297, 298, 299, 300, 301, 288, 289, 290, 291, 292, 293, 294,295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308,309, 310, 311, 312, 313, 314, 315, 302, 303, 304, 305, 306, 307, 308,309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322,323, 324, 325, 326, 327, 328, 329, 316, 317, 318, 319, 320, 321, 322,323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336,337, 338, 339, 340, 341, 342, 343, 330, 331, 332, 333, 334, 335, 336,337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350,351, 352, 353, 354, 355, 356, 357, 344, 345, 346, 347, 348, 349, 350,351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364,365, 366, 367, 368, 369, 370, 371, 358, 359, 360, 361, 362, 363, 364,365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378,379, 380, 381, 382, 383, 384, 385, 372, 373, 374, 375, 376, 377, 378,379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392,393, 394, 395, 396, 397, 398, 399, 386, 387, 388, 389, 390, 391, 392,393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406,407, 408, 409, 410, 411, 412, 413, 400, 401, 402, 403, 404, 405, 406,407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420,421, 422, 423, 424, 425, 426, 427, 414, 415, 416, 417, 418, 419, 420,421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434,435, 436, 437, 438, 439, 440, 441, 428, 429, 430, 431, 432, 433, 434,435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448,449, 450, 451, 452, 453, 454, 455, 442, 443, 444, 445, 446, 447, 448,449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462,463, 464, 465, 466, 467, 468, 469, 456, 457, 458, 459, 460, 461, 462,463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476,477, 478, 479, 480, 481, 482, 483, 470, 471, 472, 473, 474, 475, 476,477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490,491, 492, 493, 494, 495, 496, 497, 484, 485, 486, 487, 488, 489, 490,491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504,505, 506, 507, 508, 509, 510, 511, 498, 499, 500, 501, 502, 503, 504,505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518,519, 520, 521, 522, 523, 524, 525, 512, 513, 514, 515, 516, 517, 518,519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532,533, 534, 535, 536, 537, 538, 539, 526, 527, 528, 529, 530, 531, 532,533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546,547, 548, 549, 550, 551, 552, 553, 540, 541, 542, 543, 544, 545, 546,547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560,561, 562, 563, 564, 565, 566, 567, 554, 555, 556, 557, 558, 559, 560,561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574,575, 576, 577, 578, 579, 580, 581, 568, 569, 570, 571, 572, 573, 574,575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588,589, 590, 591, 592, 593, 594, 595, 582, 583, 584, 585, 586, 587, 588,589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602,603, 604, 605, 606, 607, 608, 609, 596, 597, 598, 599, 600, 601, 602,603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616,617, 618, 619, 620, 621, 622, 623, 610, 611, 612, 613, 614, 615, 616,617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630,631, 632, 633, 634, 635, 636, 637, 624, 625, 626, 627, 628, 629, 630,631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644,645, 646, 647, 648, 649, 650, 651, 638, 639, 640, 641, 642, 643, 644,645, 646 652, 653, 654

TABLE 9 Cna_B domain antigens comprising SEQ ID NO: 10(MGAS10270_Spy0113, SEQ ID NO: 26; >gi|94989622|ref|YP_597722.1|collagen adhesion protein [Streptococcus pyogenes MGAS10270]) number ofadditional contiguous amino acids of SEQ ID NO: 26 at N terminus of SEQID NO: 10 number of additional contiguous amino acids of SEQ ID NO: 26at C terminus of SEQ ID NO: 10 0-51, e.g., 0, 1, 2, 0-768, e.g., 0, 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 3, 4, 5, 6, 7, 8, 9, 33, 34,35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 10, 11, 12, 13, 14,66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 15, 16, 17,18, 19, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111,112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 20, 21, 22,23, 24, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136,137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 25, 26, 27,28, 29, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161,162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 30, 31, 32,33, 34, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186,187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 35, 36, 37,38, 39, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211,212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 40, 41, 42,43, 44, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236,237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 45, 46, 47,48, 49, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261,262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 50, 51 274,275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288,289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302,303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316,317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330,331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344,345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358,359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372,373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386,387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400,401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414,415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428,429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442,443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456,457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470,471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484,485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498,499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512,513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526,527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540,541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554,555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568,569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582,583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596,597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610,611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624,625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638,639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652,653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666,667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680,681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694,695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708,709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722,723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736,737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750,751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764,765, 766, 767, 768

TABLE 10 Cna_B domain antigens comprising SEQ ID NO: 27 (SAG_0646, SEQID NO: 45; >gi|22536815|ref|NP_687666.1| cell wall surface anchor familyprotein [Streptococcus agalactiae 2603V/R]) number of additionalcontiguous amino number of additional contiguous amino acids of SEQ IDNO: 45 acids of SEQ ID NO: 45 at C terminus of at N terminus of SEQ IDNO: 27 SEQ ID NO: 27 0-169, e.g., 0, 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 0-52, e.g., 0, 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 24, 25, 26, 27, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55,56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 42, 43, 44, 45, 46, 47, 48, 49,50, 51, 52 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101,102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115,116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129,130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143,144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157,158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169

TABLE 11 Cna_B domain antigens comprising SEQ ID NO: 28 (SAL 1482, SEQID NO: 46; GBS150 = SAL_1482 (ancillary2),jcvi.org/tigr-scripts/CMR/shared/GenePage.cgi?locus = SAL_1482 >SAL_1482 number of additional contiguous amino number of additionalcontiguous amino acids of SEQ ID NO: 46 acids of SEQ ID NO: 46 at Cterminus of at N terminus of SEQ ID NO: 28 SEQ ID NO: 28 0-160, e.g., 0,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,21, 0-75, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,42, 43, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 44, 45,46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63,64, 65, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 66, 67,68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85,86, 87, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 108,109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122,123, 124, 70, 71, 72, 73, 74, 75 125, 126, 127, 128, 129, 130, 131, 132,133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146,147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160

TABLE 12 Cna_B domain antigens comprising SEQ ID NO: 29 (SAG 0649, SEQID NO: 47; >gi|22536818|ref|NP_687669.1| cell wall surface anchor familyprotein, putative [Streptococcus agalactiae 2603V/R]) number ofadditional contiguous amino acids of SEQ ID NO: 47 at N terminus of SEQID NO: 29 number of additional contiguous amino acids of SEQ ID NO: 47at C terminus of SEQ ID NO: 29 0-51, e.g., 0, 1, 2, 3, 0-778, e.g., 0,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20,21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 4, 5, 6, 7, 8, 9, 10, 32,33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50,51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 11, 12, 13, 14, 15,64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81,82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 16, 17, 18, 19,20, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109,110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 21, 22, 23, 24,25, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133,134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 26, 27, 28, 29,30, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157,158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 31, 32, 33, 34,35, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181,182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 36, 37, 38, 39,40, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205,206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 41, 42, 43, 44,45, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229,230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 46, 47, 48, 49,50, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253,254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 51 265, 266, 267,268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281,282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295,296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309,310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323,324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337,338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351,352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365,366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379,380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393,394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407,408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421,422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435,436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449,450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463,464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477,478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491,492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505,506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519,520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533,534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547,548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561,562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575,576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589,590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603,604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617,618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631,632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645,646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659,660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673,674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687,688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701,702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715,716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729,730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743,744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757,758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771,772, 773, 774, 775, 776, 777, 778

TABLE 13 A. Cna_B domain antigens comprising SEQ ID NO: 110 or 30 (SAL1487, SEQ ID NO: 48; GBS67 = SAL_1487 (ancillary 1),jcvi.org/cgi-bin/CMR/shared/GenePage.cgi?locus = SAL_1487 > SAL_1487number of additional contiguous amino acids of SEQ ID NO: 48 at Nterminus of SEQ ID number of additional contiguous amino acids of SEQ IDNO: 48 NO: 110 or 30 at C terminus of SEQ ID NO: 110 or 30 0-52, e.g.,0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 0-786, e.g., 0, 1, 2, 3, 4, 5, 6,7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 11, 12, 13, 14, 15, 16, 17, 18, 19,20, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34,35, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 36, 37, 38, 39, 40, 41, 42,43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 31, 32, 33, 34, 35, 36, 37,38, 39, 40, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68,69, 70, 71, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 72, 73, 74, 75, 76,77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 51, 52 90, 91, 92,93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108,109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122,123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136,137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150,151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164,165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178,179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192,193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206,207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220,221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234,235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248,249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262,263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276,277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290,291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304,305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318,319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332,333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346,347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360,361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374,375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388,389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402,403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416,417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430,431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444,445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458,459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472,473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486,487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500,501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514,515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528,529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542,543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556,557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570,571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584,585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598,599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612,613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626,627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640,641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654,655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668,669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682,683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696,697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710,711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724,725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738,739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752,753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766,767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780,781, 782, 783, 784, 785, 786 B. Cna_B domain antigens comprising SEQ IDNO: 111 (SAL 1487, SEQ ID NO: 48; GBS67 = SAL_1487 (ancillary 1),jcvi.org/cgi-bin/CMR/shared/GenePage.cgi?locus = SAL_1487 > SAL_1487number of additional contiguous amino acids of number of additionalcontiguous amino acids of SEQ ID NO: 48 at SEQ ID NO: 48 at C terminus Nterminus of SEQ ID NO: 111 of SEQ ID NO: 111 0-750, e.g., 0, 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 0-67, e.g., 0, 1, 2, 3,4, 5, 6, 7, 8, 9, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 36, 37, 38,39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64,65, 66, 67, 68, 69, 70, 71, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 72,73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 40,41, 42, 43, 44, 45, 46, 47, 48, 49, 90, 91, 92, 93, 94, 95, 96, 97, 98,99, 100, 101, 102, 103, 104, 105, 50, 51, 52, 53, 54, 55, 56, 57, 58,59, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118,119, 60, 61, 62, 63, 64, 65, 66, 67 120, 121, 122, 123, 124, 125, 126,127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140,141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154,155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168,169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196,197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210,211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224,225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238,239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252,253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266,267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294,295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308,309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322,323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336,337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350,351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364,365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378,379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392,393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406,407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420,421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434,435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448,449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462,463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476,477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490,491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504,505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518,519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532,533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546,547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560,561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574,575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588,589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602,603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616,617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630,631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644,645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658,659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672,673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686,687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700,701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714,715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728,729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742,743, 744, 745, 746, 747, 748, 749, 750

TABLE 14 Cna_B domain antigens comprising SEQ ID NO: 31 or 113 (SAN1518, SEQ ID NO: 49; >ORF01523 cell wall surface anchor family protein,putative {Streptococcus agalactiae COH1}) number of additionalcontiguous amino acids of SEQ ID NO: 49 number of additional contiguousamino acids of at N terminus of SEQ ID NO: 31 or 113 SEQ ID NO: 49 at Cterminus of SEQ ID NO: 31 or 113 0-365, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 0-50, e.g., 0, 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 36, 37, 38, 39, 40, 41, 42, 43, 44,45, 46, 47, 48, 49, 50, 51, 52, 53, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47, 48, 49, 50 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64,65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82,83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142,143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156,157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170,171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198,199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212,213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226,227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240,241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254,255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268,269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282,283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296,297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310,311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324,325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338,339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352,353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365

TABLE 15 Cna_B domain antigens comprising SEQ ID NO: 32 (SAN 1519, SEQID NO: 50; >ORF01524 reticulocyte binding protein {Streptococcusagalactiae COH1}) number of additional contiguous amino number ofadditional contiguous amino acids of SEQ ID NO: 50 acids of SEQ ID NO:50 at C terminus of at N terminus of SEQ ID NO: 32 SEQ ID NO: 32 0-1290,e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17,0-62, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 18, 19, 20,21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 36, 37, 38, 39, 40, 41, 42,43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 28, 29, 30, 31, 32, 33, 34,35, 36, 37, 38, 39, 40, 41, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64,65, 66, 67, 68, 69, 70, 71, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,53, 54, 55, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86,87, 88, 89, 56, 57, 58, 59, 60, 61, 62 90, 91, 92, 93, 94, 95, 96, 97,98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112,113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126,127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140,141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154,155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168,169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196,197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210,211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224,225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238,239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252,253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266,267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294,295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308,309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322,323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336,337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350,351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364,365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378,379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392,393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406,407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420,421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434,435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448,449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462,463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476,477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490,491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504,505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518,519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532,533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546,547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560,561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574,575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588,589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602,603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616,617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630,631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644,645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658,659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672,673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686,687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700,701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714,715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728,729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742,743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756,757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770,771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784,785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798,799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812,813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826,827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840,841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854,855, 856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868,869, 870, 871, 872, 873, 874, 875, 876, 877, 878, 879, 880, 881, 882,883, 884, 885, 886, 887, 888, 889, 890, 891, 892, 893, 894, 895, 896,897, 898, 899, 900, 901, 902, 903, 904, 905, 906, 907, 908, 909, 910,911, 912, 913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924,925, 926, 927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937, 938,939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952,953, 954, 955, 956, 957, 958, 959, 960, 961, 962, 963, 964, 965, 966,967, 968, 969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980,981, 982, 983, 984, 985, 986, 987, 988, 989, 990, 991, 992, 993, 994,995, 996, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006, 1007,1008, 1009, 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018, 1019,1020, 1021, 1022, 1023, 1024, 1025, 1026, 1027, 1028, 1029, 1030, 1031,1032, 1033, 1034, 1035, 1036, 1037, 1038, 1039, 1040, 1041, 1042, 1043,1044, 1045, 1046, 1047, 1048, 1049, 1050, 1051, 1052, 1053, 1054, 1055,1056, 1057, 1058, 1059, 1060, 1061, 1062, 1063, 1064, 1065, 1066, 1067,1068, 1069, 1070, 1071, 1072, 1073, 1074, 1075, 1076, 1077, 1078, 1079,1080, 1081, 1082, 1083, 1084, 1085, 1086, 1087, 1088, 1089, 1090, 1091,1092, 1093, 1094, 1095, 1096, 1097, 1098, 1099, 1100, 1101, 1102, 1103,1104, 1105, 1106, 1107, 1108, 1109, 1110, 1111, 1112, 1113, 1114, 1115,1116, 1117, 1118, 1119, 1120, 1121, 1122, 1123, 1124, 1125, 1126, 1127,1128, 1129, 1130, 1131, 1132, 1133, 1134, 1135, 1136, 1137, 1138, 1139,1140, 1141, 1142, 1143, 1144, 1145, 1146, 1147, 1148, 1149, 1150, 1151,1152, 1153, 1154, 1155, 1156, 1157, 1158, 1159, 1160, 1161, 1162, 1163,1164, 1165, 1166, 1167, 1168, 1169, 1170, 1171, 1172, 1173, 1174, 1175,1176, 1177, 1178, 1179, 1180, 1181, 1182, 1183, 1184, 1185, 1186, 1187,1188, 1189, 1190, 1191, 1192, 1193, 1194, 1195, 1196, 1197, 1198, 1199,1200, 1201, 1202, 1203, 1204, 1205, 1206, 1207, 1208, 1209, 1210, 1211,1212, 1213, 1214, 1215, 1216, 1217, 1218, 1219, 1220, 1221, 1222, 1223,1224, 1225, 1226, 1227, 1228, 1229, 1230, 1231, 1232, 1233, 1234, 1235,1236, 1237, 1238, 1239, 1240, 1241, 1242, 1243, 1244, 1245, 1246, 1247,1248, 1249, 1250, 1251, 1252, 1253, 1254, 1255, 1256, 1257, 1258, 1259,1260, 1261, 1262, 1263, 1264, 1265, 1266, 1267, 1268, 1269, 1270, 1271,1272, 1273, 1274, 1275, 1276, 1277, 1278, 1279, 1280, 1281, 1282, 1283,1284, 1285, 1286, 1287, 1288, 1289, 1290

TABLE 16 Cna_B domain antigens comprising SEQ ID NO: 33 or 112 (SAG0645, SEQ ID NO: 51; >gi|22536814|ref|NP_687665.1| cell wall surfaceanchor family protein [Streptococcus agalactiae 2603V/R]) number ofadditional contiguous amino acids number of additional contiguous aminoacids of SEQ ID NO: 51 of SEQ ID NO: 51 at C terminus of SEQ ID at Nterminus of SEQ ID NO: 33 or 112 NO: 33 or 112 0-394, e.g., 0, 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 0-65, e.g., 0, 1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 15, 16, 17, 18, 19, 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46,47, 48, 49, 50, 51, 52, 53, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40,41, 42, 43, 44, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67,68, 69, 70, 71, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58,59, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88,89, 60, 61, 62, 63, 64, 65 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142,143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156,157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170,171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198,199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212,213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226,227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240,241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254,255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268,269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282,283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296,297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310,311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324,325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338,339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352,353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366,367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380,381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394

TABLE 17 Cna_B domain antigens comprising SEQ ID NO: 35 (SAN 1516, SEQID NO: 52; >ORF01521 hypothetical protein {Streptococcus agalactiaeCOH1}) number of additional contiguous amino acids of SEQ ID number ofadditional contiguous amino acids of SEQ ID NO: 52 NO: 52 at N terminusof SEQ ID NO: 35 at C terminus of SEQ ID NO: 35 0-98, e.g., 0, 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 0-36, e.g., 0, 1, 2,3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 18, 19, 20, 21, 22,23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 36, 37, 38, 39, 40, 41,42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 35, 36 54, 55, 56, 57,58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75,76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93,94, 95, 96, 97, 98

TABLE 18 A. Cna_B domain antigens comprising SEQ ID NO: 114 (SAL 1486,SEQ ID NO: 102; GBS59 = SAL_1486 (backbone),jcvi.org/cgi-bin/CMR/shared/GenePage.cgi?locus = SAL_1486 > SAL_1486number of additional contiguous amino acids of SEQ ID NO: 102 at numberof additional contiguous amino acids of SEQ ID NO: 102 N terminus of SEQID NO: 114 at C terminus of SEQ ID NO: 114 0-83, e.g., 0, 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 0-503, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, 17, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 18, 19, 20,21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46,47, 48, 49, 50, 51, 52, 53, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 54,55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 41,42, 43, 44, 45, 46, 47, 48, 49, 50, 72, 73, 74, 75, 76, 77, 78, 79, 80,81, 82, 83, 84, 85, 86, 87, 88, 89, 51, 52, 53, 54, 55, 56, 57, 58, 59,60, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104,105, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 106, 107, 108, 109, 110,111, 112, 113, 114, 115, 116, 117, 118, 119, 71, 72, 73, 74, 75, 76, 77,78, 79, 80, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131,132, 133, 81, 82, 83 134, 135, 136, 137, 138, 139, 140, 141, 142, 143,144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157,158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171,172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185,186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199,200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213,214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227,228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241,242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255,256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283,284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297,298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311,312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325,326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339,340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353,354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367,368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381,382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395,396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409,410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423,424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437,438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451,452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465,466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479,480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493,494, 495, 496, 497, 498, 499, 500, 501, 502, 503 B. Cna_B domainantigens comprising SEQ ID NO: 115 (SAL 1486, SEQ ID NO: 102; GBS59 =SAL_1486 (backbone), jcvi.org/cgi-bin/CMR/shared/GenePage.cgi?locus =SAL_1486 > SAL_1486 number of additional contiguous amino acids ofnumber of additional contiguous amino acids of SEQ ID NO: 102 SEQ ID NO:102 at C at N terminus of SEQ ID NO: 115 terminus of SEQ ID NO: 1150-470, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 0-56, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49,50, 51, 52, 53, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 54, 55, 56, 57,58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 31, 32, 33, 34,35, 36, 37, 38, 39, 40, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 90, 91,92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 51, 52,53, 54, 55, 56 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116,117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130,131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144,145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158,159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172,173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186,187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200,201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214,215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228,229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242,243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256,257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270,271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284,285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298,299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312,313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326,327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340,341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354,355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368,369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382,383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396,397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410,411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424,425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438,439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452,453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466,467, 468, 469, 470 C. Cna_B domain antigens comprising SEQ ID NO: 116(SAG 1407, SEQ ID NO: 118) number of additional contiguous amino acidsof SEQ ID NO: 118 at N terminus of SEQ ID number of additionalcontiguous amino acids of SEQ ID NO: 118 NO: 116 at C terminus of SEQ IDNO: 116 0-20, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 0-614, e.g., 0, 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 11, 12, 13, 14,15, 16, 17, 18, 19, 20 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47,48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142,143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156,157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170,171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198,199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212,213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226,227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240,241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254,255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268,269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282,283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296,297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310,311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324,325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338,339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352,353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366,367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380,381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394,395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408,409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422,423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436,437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450,451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464,465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478,479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492,493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506,507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520,521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534,535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548,549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562,563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576,577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590,591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604,605, 606, 607, 608, 609, 610, 611, 612, 613, 614 D. Cna_B domainantigens comprising SEQ ID NO: 117 (SAG 1407, SEQ ID NO: 118) number ofadditional contiguous amino number of additional contiguous amino acidsof SEQ ID NO: 118 acids of SEQ ID NO: 118 at C terminus at N terminus ofSEQ ID NO: 117 of SEQ ID NO: 117 0-489, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 0-53, e.g., 0, 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31,32, 33, 34, 35, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 36, 37, 38, 39,40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 21, 22, 23, 24,25, 26, 27, 28, 29, 30, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 70, 71, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 72, 73,74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 41, 42,43, 44, 45, 46, 47, 48, 49, 50, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99,100, 101, 102, 103, 104, 105, 51, 52, 53 106, 107, 108, 109, 110, 111,112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125,126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139,140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153,154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167,168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181,182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195,196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209,210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223,224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237,238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251,252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265,266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279,280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293,294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307,308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321,322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335,336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349,350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363,364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377,378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391,392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405,406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419,420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433,434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447,448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461,462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475,476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489

TABLE 19 Cna_B domain antigens comprising SEQ ID NO: 53 (SP_0463, SEQ IDNO: 63; >gi|15900379|ref|NP_344983.1| cell wall surface anchor familyprotein [Streptococcus pneumoniae TIGR4]) number of additionalcontiguous amino acids of SEQ ID NO: 63 at number of additionalcontiguous amino acids of SEQ ID NO: 63 at N terminus of SEQ ID NO: 53 Cterminus of SEQ ID NO: 53 0-459, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 0-68, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 30, 31, 32, 33, 34,35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,53, 54, 55, 56, 57, 58, 59, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 22, 23, 24, 25, 26, 27,28, 29, 30, 31, 32, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101,102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 33, 34,35, 36, 37, 38, 39, 40, 41, 42, 43, 115, 116, 117, 118, 119, 120, 121,122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135,136, 137, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 138, 139, 140,141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154,155, 156, 157, 158, 159, 160, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64,65, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173,174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 66, 67, 68 184, 185,186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199,200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213,214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227,228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241,242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255,256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283,284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297,298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311,312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325,326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339,340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353,354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367,368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381,382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395,396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409,410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423,424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437,438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451,452, 453, 454, 455, 456, 457, 458, 459

TABLE 20 Cna_B domain antigens comprising SEQ ID NO: 54 (SP_0462, SEQ IDNO: 64; >gi|15900378|ref|NP_344982.1| cell wall surface anchor familyprotein [Streptococcus pneumoniae TIGR4]) number of additionalcontiguous amino acids of SEQ ID NO: 64 at N terminus of SEQ ID NO: 54number of additional contiguous amino acids of SEQ ID NO: 64 at Cterminus of SEQ ID NO: 54 0-60, e.g., 0, 1, 0-762, e.g., 0, 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 2, 3, 4, 5, 6, 36, 37,38, 39,40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55,56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 7, 8, 9,10, 11, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87,88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104,105, 12, 13, 14, 15, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115,116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129,130, 131, 132, 16, 17, 18, 19, 133, 134, 135, 136, 137, 138, 139, 140,141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154,155, 156, 157, 158, 159, 20, 21, 22, 23, 160, 161, 162, 163, 164, 165,166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179,180, 181, 182, 183, 184, 185, 186, 24, 25, 26, 27, 187, 188, 189, 190,191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204,205, 206, 207, 208, 209, 210, 211, 212, 213, 28, 29, 30, 31, 214, 215,216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229,230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 32, 33, 34, 35,241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254,255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 36, 37,38, 39, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294,40, 41, 42, 43, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305,306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319,320, 321, 44, 45, 46, 47, 322, 323, 324, 325, 326, 327, 328, 329, 330,331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344,345, 346, 347, 348, 48, 49, 50, 51, 349, 350, 351, 352, 353, 354, 355,356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369,370, 371, 372, 373, 374, 375, 52, 53, 54, 55, 376, 377, 378, 379, 380,381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394,395, 396, 397, 398, 399, 400, 401, 402, 56, 57, 58, 59, 403, 404, 405,406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419,420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 60 430, 431, 432, 433,434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447,448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461,462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475,476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489,490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503,504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517,518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531,532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545,546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559,560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573,574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587,588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601,602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615,616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629,630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643,644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657,658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671,672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685,686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699,700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713,714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727,728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741,742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755,756, 757, 758, 759, 760, 761, 762

TABLE 21 Cna_B domain antigens comprising SEQ ID NO: 55 (SP_0464, SEQ IDNO: 65; >gi|15900380|ref|NP_344984.1| cell wall surface anchor familyprotein [Streptococcus pneumoniae TIGR4]) number of additionalcontiguous amino acids of SEQ ID NO: 65 at C number of additionalcontiguous amino acids of SEQ ID NO: 65 at N terminus of SEQ ID NO: 55terminus of SEQ ID NO: 55 0-271, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 0-41, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51,52, 53, 54, 55, 56, 57, 58, 59, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75,76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 24, 25, 26, 27,28, 29, 30, 31, 32, 33, 34, 35, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99,100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113,114, 36, 37, 38, 39, 40, 41 115, 116, 117, 118, 119, 120, 121, 122, 123,124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137,138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151,152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165,166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179,180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193,194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207,208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221,222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235,236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249,250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263,264, 265, 266, 267, 268, 269, 270, 271

TABLE 22 Cna_B domain antigens comprising SEQ ID NO: 66 (SdrD MW0517,SEQ ID NO: 72); >gi|21282246|ref|NP_645334.1| Ser- Asp richfibrinogen-binding bone sialoprotein-binding protein [Staphylococcusaureus subsp. aureus MW2]) number of additional contiguous amino acidsof SEQ ID NO: 72 at N number of additional contiguous amino acids of SEQterminus of SEQ ID NO: 66 ID NO: 72 at C terminus of SEQ ID NO: 660-703, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 0-473, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 18, 19, 20, 21,22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 48, 49, 50, 51,52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69,70, 71, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51,52, 53, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87,88, 89, 90, 91, 92, 93, 94, 95, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63,64, 65, 66, 67, 68, 69, 70, 71, 96, 97, 98, 99, 100, 101, 102, 103, 104,105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 72, 73, 74, 75, 76,77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 115, 116, 117, 118,119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146,147, 148, 149, 150, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115,116, 117, 118, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161,162, 163, 164, 165, 166, 167, 168, 119, 120, 121, 122, 123, 124, 125,126, 127, 128, 129, 130, 131, 169, 170, 171, 172, 173, 174, 175, 176,177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 132, 133, 134, 135,136, 137, 138, 139, 140, 141, 142, 143, 144, 187, 188, 189, 190, 191,192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 145,146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 205, 206,207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220,221, 222, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169,170, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235,236, 237, 238, 239, 240, 171, 172, 173, 174, 175, 176, 177, 178, 179,180, 181, 182, 183, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250,251, 252, 253, 254, 255, 256, 257, 258, 184, 185, 186, 187, 188, 189,190, 191, 192, 193, 194, 195, 196, 259, 260, 261, 262, 263, 264, 265,266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 197, 198, 199,200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294,210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 295,296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309,310, 311, 312, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233,234, 235, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324,325, 326, 327, 328, 329, 330, 236, 237, 238, 239, 240, 241, 242, 243,244, 245, 246, 247, 248, 331, 332, 333, 334, 335, 336, 337, 338, 339,340, 341, 342, 343, 344, 345, 346, 347, 348, 249, 250, 251, 252, 253,254, 255, 256, 257, 258, 259, 260, 261, 349, 350, 351, 352, 353, 354,355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 262, 263,264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 367, 368, 369,370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383,384, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287,385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398,399, 400, 401, 402, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297,298, 299, 300, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413,414, 415, 416, 417, 418, 419, 420, 301, 302, 303, 304, 305, 306, 307,308, 309, 310, 311, 312, 313, 421, 422, 423, 424, 425, 426, 427, 428,429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 314, 315, 316, 317,318, 319, 320, 321, 322, 323, 324, 325, 326, 439, 440, 441, 442, 443,444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 327,328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 457, 458,459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472,473, 474, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351,352, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487,488, 489, 490, 491, 492, 353, 354, 355, 356, 357, 358, 359, 360, 361,362, 363, 364, 365, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502,503, 504, 505, 506, 507, 508, 509, 510, 366, 367, 368, 369, 370, 371,372, 373, 374, 375, 376, 377, 378, 511, 512, 513, 514, 515, 516, 517,518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 379, 380, 381,382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 529, 530, 531, 532,533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546,392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 547,548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561,562, 563, 564, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415,416, 417, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576,577, 578, 579, 580, 581, 582, 418, 419, 420, 421, 422, 423, 424, 425,426, 427, 428, 429, 430, 583, 584, 585, 586, 587, 588, 589, 590, 591,592, 593, 594, 595, 596, 597, 598, 599, 600, 431, 432, 433, 434, 435,436, 437, 438, 439, 440, 441, 442, 443, 601, 602, 603, 604, 605, 606,607, 608, 609, 610, 611, 612 ,613, 614, 615, 616 ,617, 618, 444, 445,446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 619, 620, 621,622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635,636, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469,637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650,651, 652, 653, 654, 470, 471, 472, 473 655, 656, 657, 658, 659, 660,661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674,675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688,689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702,703

TABLE 23 Cna_B domain antigens comprising SEQ ID NO: 67 (SdrD MW0517,SEQ ID NO: 72); >gi|21282246|ref|NP_645334.1_| Ser- Asp richfibrinogen-binding bone sialoprotein-binding protein [Staphylococcusaureus subsp. aureus MW2]) number of additional contiguous amino acidsof SEQ ID NO: 72 at C number of additional contiguous amino acids of SEQID NO: 72 at N terminus of SEQ ID NO: 67 terminus of SEQ ID NO: 670-924, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 0-353, e.g., 0, 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40,41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58,59, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 90,91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106,107, 108, 109, 110, 111, 112, 113, 114, 33, 34, 35, 36, 37, 38, 39, 40,41, 42, 43, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126,127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 44, 45, 46, 47,48, 49, 50, 51, 52, 53, 54, 138, 139, 140, 141, 142, 143, 144, 145, 146,147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160,55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 161, 162, 163, 164, 165,166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179,180, 181, 182, 183, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 184,185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198,199, 200, 201, 202, 203, 204, 205, 206, 77, 78, 79, 80, 81, 82, 83, 84,85, 86, 87, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218,219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 88, 89, 90, 91,92, 93, 94, 95, 96, 97, 98, 230, 231, 232, 233, 234, 235, 236, 237, 238,239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252,99, 100, 101, 102, 103, 104, 105, 106, 253, 254, 255, 256, 257, 258,259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272,273, 274, 275, 107, 108, 109, 110, 111, 112, 113, 114, 276, 277, 278,279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292,293, 294, 295, 296, 297, 298, 115, 116, 117, 118, 119, 120, 121, 122,299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312,313, 314, 315, 316, 317, 318, 319, 320, 321, 123, 124, 125, 126, 127,128, 129, 130, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332,333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 131, 132,133, 134, 135, 136, 137, 138, 345, 346, 347, 348, 349, 350, 351, 352,353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366,367, 139, 140, 141, 142, 143, 144, 145, 146, 368, 369, 370, 371, 372,373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386,387, 388, 389, 390, 147, 148, 149, 150, 151, 152, 153, 154, 391, 392,393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406,407, 408, 409, 410, 411, 412, 413, 155, 156, 157, 158, 159, 160, 161,162, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426,427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 163, 164, 165, 166,167, 168, 169, 170, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446,447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 171,172, 173, 174, 175, 176, 177, 178, 460, 461, 462, 463, 464, 465, 466,467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480,481, 482, 179, 180, 181, 182, 183, 184, 185, 186, 483, 484, 485, 486,487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500,501, 502, 503, 504, 505, 187, 188, 189, 190, 191, 192, 193, 194, 506,507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520,521, 522, 523, 524, 525, 526, 527, 528, 195, 196, 197, 198, 199, 200,201, 202, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540,541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 203, 204, 205,206, 207, 208, 209, 210, 552, 553, 554, 555, 556, 557, 558, 559, 560,561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574,211, 212, 213, 214, 215, 216, 217, 218, 575, 576, 577, 578, 579, 580,581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594,595, 596, 597, 219, 220, 221, 222, 223, 224, 225, 226, 598, 599, 600,601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614,615, 616, 617, 618, 619, 620, 227, 228, 229, 230, 231, 232, 233, 234,621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634,635, 636, 637, 638, 639, 640, 641, 642, 643, 235, 236, 237, 238, 239,240, 241, 242, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654,655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 243, 244,245, 246, 247, 248, 249, 250, 667, 668, 669, 670, 671, 672, 673, 674,675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688,689, 251, 252, 253, 254, 255, 256, 257, 258, 690, 691, 692, 693, 694,695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708,709, 710, 711, 712, 259, 260, 261, 262, 263, 264, 265, 266, 713, 714,715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728,729, 730, 731, 732, 733, 734, 735, 267, 268, 269, 270, 271, 272, 273,274, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748,749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 275, 276, 277, 278,279, 280, 281, 282, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768,769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 283,284, 285, 286, 287, 288, 289, 290, 782, 783, 784, 785, 786, 787, 788,789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802,803, 804, 291, 292, 293, 294, 295, 296, 297, 298, 805, 806, 807, 808,809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 820, 821, 822,823, 824, 825, 826, 827, 299, 300, 301, 302, 303, 304, 305, 306, 828,829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842,843, 844, 845, 846, 847, 848, 849, 850, 307, 308, 309, 310, 311, 312,313, 314, 851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861, 862,863, 864, 865, 866, 867, 868, 869, 870, 871, 872, 873, 315, 316, 317,318, 319, 320, 321, 322, 874, 875, 876, 877, 878, 879, 880, 881, 882,883, 884, 885, 886, 887, 888, 889, 890, 891, 892, 893, 894, 895, 896,323, 324, 325, 326, 327, 328, 329, 330, 897, 898, 899, 900, 901, 902,903, 904, 905, 906, 907, 908, 909, 910, 911, 912, 913, 914, 915, 916,917, 918, 919, 331, 332, 333, 334, 335, 336, 337, 338, 920, 921, 922,923, 924 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350,351, 352, 353

TABLE 24 Cna_B domain antigens comprising SEQ ID NO: 68 (MW2612, SEQ IDNO: 73; >gi|21284341|ref|NP_647429.1| collagen adhesin precursor[Staphylococcus aureus subsp. aureus MW2]) number of additionalcontiguous amino acids of SEQ ID NO: 73 at N terminus of SEQ ID NO: 68number of additional contiguous amino acids of SEQ ID NO: 73 at Cterminus of SEQ ID NO: 68 0-344, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 0-761, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39,40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 58, 59, 60, 61, 62, 63,64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81,82, 83, 84, 85, 86, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 87,88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104,105, 106, 107, 108, 109, 110, 111, 48, 49, 50, 51, 52, 53, 54, 55, 56,57, 58, 59, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123,124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 60, 61, 62, 63, 64,65, 66, 67, 68, 69, 70, 71, 134, 135, 136, 137, 138, 139, 140, 141, 142,143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 72, 73,74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 156, 157, 158, 159, 160, 161,162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175,176, 177, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 178, 179, 180,181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194,195, 196, 197, 198, 199, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213,214, 215, 216, 217, 218, 219, 220, 221, 106, 107, 108, 109, 110, 111,112, 113, 114, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232,233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 115, 116, 117,118, 119, 120, 121, 122, 123, 244, 245, 246, 247, 248, 249, 250, 251,252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265,124, 125, 126, 127, 128, 129, 130, 131, 132, 266, 267, 268, 269, 270,271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284,285, 286, 287, 133, 134, 135, 136, 137, 138, 139, 140, 141, 288, 289,290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303,304, 305, 306, 307, 308, 309, 142, 143, 144, 145, 146, 147, 148, 149,150, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322,323, 324, 325, 326, 327, 328, 329, 330, 331, 151, 152, 153, 154, 155,156, 157, 158, 159, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341,342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 160, 161,162, 163, 164, 165, 166, 167, 168, 354, 355, 356, 357, 358, 359, 360,361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374,375, 169, 170, 171, 172, 173, 174, 175, 176, 177, 376, 377, 378, 379,380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393,394, 395, 396, 397, 178, 179, 180, 181, 182, 183, 184, 185, 186, 398,399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412,413, 414, 415, 416, 417, 418, 419, 187, 188, 189, 190, 191, 192, 193,194, 195, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431,432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 196, 197, 198, 199,200, 201, 202, 203, 204, 442, 443, 444, 445, 446, 447, 448, 449, 450,451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 205,206, 207, 208, 209, 210, 211, 212, 213, 464, 465, 466, 467, 468, 469,470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483,484, 485, 214, 215, 216, 217, 218, 219, 220, 221, 222, 486, 487, 488,489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502,503, 504, 505, 506, 507, 223, 224, 225, 226, 227, 228, 229, 230, 231,508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521,522, 523, 524, 525, 526, 527, 528, 529, 232, 233, 234, 235, 236, 237,238, 239, 240, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540,541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 241, 242, 243,244, 245, 246, 247, 248, 249, 552, 553, 554, 555, 556, 557, 558, 559,560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573,250, 251, 252, 253, 254, 255, 256, 257, 258, 574, 575, 576, 577, 578,579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592,593, 594, 595, 259, 260, 261, 262, 263, 264, 265, 266, 267, 596, 597,598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611,612, 613, 614, 615, 616, 617, 268, 269, 270, 271, 272, 273, 274, 275,276, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630,631, 632, 633, 634, 635, 636, 637, 638, 639, 277, 278, 279, 280, 281,282, 283, 284, 285, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649,650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 286, 287,288, 289, 290, 291, 292, 293, 294, 662, 663, 664, 665, 666, 667, 668,669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682,683, 295, 296, 297, 298, 299, 300, 301, 302, 303, 684, 685, 686, 687,688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701,702, 703, 704, 705, 304, 305, 306, 307, 308, 309, 310, 311, 312, 706,707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720,721, 722, 723, 724, 725, 726, 727, 313, 314, 315, 316, 317, 318, 319,320, 321, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739,740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 322, 323, 324, 325,326, 327, 328, 329, 330, 750, 751, 752, 753, 754, 755, 756, 757, 758,759, 760, 761 331, 332, 333, 334, 335, 336, 337, 338 ,339, 340, 341,342, 343, 344

TABLE 25 Cna_B domain antigens comprising SEQ ID NO: 1 (Spy_M18_0126,SEQ ID NO: 23; >gi|19745301|ref|NP_606437.1| putative collagen bindingprotein [Streptococcus pyogenes MGAS8232]) number of additionalcontiguous amino acids of SEQ ID NO: 23 at N terminus of SEQ ID NO: 1number of additional contiguous amino acids of SEQ ID NO: 23 at Cterminus of SEQ ID NO: 1 0-70, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 0-282, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39,40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 58, 59, 60, 61, 62, 63,64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81,82, 83, 84, 85, 86, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 87,88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104,105, 106, 107, 108, 109, 110, 111, 48, 49, 50, 51, 52, 53, 54, 55, 56,57, 58, 59, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123,124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 60, 61, 62, 63, 64,65, 66, 67, 68, 69, 70 134, 135, 136, 137, 138, 139, 140, 141, 142, 143,144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157,158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171,172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185,186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199,200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213,214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227,228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241,242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255,256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282

TABLE 26 Cna_B domain antigens comprising SEQ ID NO: 34(SAG 0649, SEQ IDNO: 47; >gi|22536818|ref|NP_687669.1| cell wall surface anchor familyprotein, putative [Streptococcus agalactiae 2603V/R]) number ofadditional contiguous amino acids of SEQ ID NO: 47 at C terminus ofnumber of additional contiguous amino acids of SEQ ID NO: 47 at Nterminus of SEQ ID NO: 34 SEQ ID NO: 34 0-748, e.g., 0, 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24,25, 26, 27, 0-62, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45,46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 24, 25, 26, 27, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67,68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 28, 29,30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55,109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122,123, 124, 125, 126, 127, 128, 129, 56, 57, 58, 59, 60, 61, 62 130, 131,132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145,146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159,160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173,174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187,188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201,202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215,216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229,230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243,244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257,258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271,272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285,286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299,300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313,314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327,328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341,342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355,356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369,370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383,384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397,398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411,412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425,426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439,440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453,454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467,468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481,482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495,496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509,510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523,524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537,538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551,552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565,566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579,580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593,594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607,608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621,622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635,636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649,650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663,664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677,678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691,692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705,706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719,720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733,734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747,748

TABLE 27 Cna_B domain antigens comprising SEQ ID NO: 57 (S. pneumoniaeprotein SP_0464; SEQ ID NO: 65) number of additional contiguous aminoacids of SEQ ID number of additional contiguous amino acids of SEQ IDNO: 65 at C NO: 65 at N terminus of SEQ ID NO: 57 terminus of SEQ ID NO:57 0-161, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 0-141, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,29, 30, 31, 32, 33, 34, 35, 36, 37, 22, 23, 24, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 38, 39, 40, 41, 42,43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 44, 45, 46, 47,48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74,75, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82,83, 84, 85, 86, 87, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88,89, 90, 91, 92, 93, 94, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99,100, 101, 102, 103, 104, 105, 106, 107, 95, 96, 97, 98, 99, 100, 101,102, 103, 104, 105, 106, 107, 108, 109, 108, 109, 110, 111, 112, 113,114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 110, 111, 112,113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 125, 126, 127,128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137,138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151,152, 153, 154, 155, 156, 157, 158, 159, 160, 161

TABLE 28 Cna_B domain antigens comprising SEQ ID NO: 80 (S. suis proteinSSU05_0474[Streptococcus suis 05ZYH33; SEQ ID NO: 82) number ofadditional contiguous amino acids of SEQ ID NO: 82 at C terminus numberof additional contiguous amino acids of SEQ ID NO: 82 at N terminus ofSEQ ID NO: 80 of SEQ ID NO: 80 0-348, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,27, 28, 0-53, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 29, 30,31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,49, 50, 51, 52, 53, 54, 55, 56, 57, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 24, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72,73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 25, 26, 27, 28,29, 30, 31, 32, 33, 34, 35, 36, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96,97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111,37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 112, 113, 114, 115, 116,117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130,131, 132, 49, 50, 51, 52, 53 133, 134, 135, 136, 137, 138, 139, 140,141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154,155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168,169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196,197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210,211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224,225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238,239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252,253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266,267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294,295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308,309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322,323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336,337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348

TABLE 29 Cna_B domain antigens comprising SEQ ID NO: 81 (S. suis proteinDUF11: Surface protein from Gram-positive cocci, anchor region[Streptococcus suis 89/1591; SEQ ID NO: 83) number of additionalcontiguous amino acids of SEQ ID NO: 83 at C number of additionalcontiguous amino acids of SEQ ID NO: 83 at N terminus of SEQ ID NO: 81terminus of SEQ ID NO: 81 0-358, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28,0-124, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51,52, 53, 54, 55, 56, 57, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75,76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 24, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99,100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 36, 37, 38,39, 40, 41, 42, 43, 44, 45, 46, 47, 112, 113, 114, 115, 116, 117, 118,119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132,133, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 134, 135, 136, 137,138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151,152, 153, 154, 155, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 156,157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170,171, 172, 173, 174, 175, 176, 177, 72, 73, 74, 75, 76, 77, 78, 79, 80,81, 82, 83, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189,190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 84, 85, 86, 87, 88,89, 90, 91, 92, 93, 94, 95, 200, 201, 202, 203, 204, 205, 206, 207, 208,209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 96, 97,98, 99, 100, 101, 102, 103, 104, 105, 222, 223, 224, 225, 226, 227, 228,229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242,243, 106, 107, 108, 109, 110, 111, 112, 113, 114, 244, 245, 246, 247,248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261,262, 263, 264, 265, 115, 116, 117, 118, 119, 120, 121, 122, 123, 266,267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 124 288, 289, 290, 291, 292, 293,294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307,308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321,322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335,336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349,350, 351, 352, 353, 354, 355, 356, 357, 358

TABLE 30 Cna_B domain antigens comprising SEQ ID NO: 84 (S. equi proteinancillary protein SEQ0935 undefined product 914186:916159 forwardMW:73872 67; SEQ ID NO: 87) number of additional contiguous amino acidsof SEQ ID NO: 87 at N number of additional contiguous amino acids of SEQterminus of SEQ ID NO: 84 ID NO: 87 at C terminus of SEQ ID NO: 840-350, e.g. 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 0-244, e.g. 0, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 18, 19, 20, 21,22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 48, 49, 50, 51, 52,53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70,71, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63,64, 65, 66, 67, 68, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106,107, 108, 109, 110, 111, 112, 113, 114, 69, 70, 71, 72, 73, 74, 75, 76,77, 78, 79, 80, 81, 82, 83, 84, 85, 115, 116, 117, 118, 119, 120, 121,122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 86, 87, 88, 89,90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 133, 134, 135, 136,137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150,102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 151,152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165,166, 167, 168, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125,126, 127, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180,181, 182, 183, 184, 185, 186, 128, 129, 130, 131, 132, 133, 134, 135,136, 137, 138, 139, 140, 187, 188, 189, 190, 191, 192, 193, 194, 195,196, 197, 198, 199, 200, 201, 202, 203, 204, 141, 142, 143, 144, 145,146, 147, 148, 149, 150, 151, 152, 153, 205, 206, 207, 208, 209, 210,211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 154, 155,156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 223, 224, 225,226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239,240, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179,241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254,255, 256, 257, 258, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189,190, 191, 192, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 193, 194, 195, 196, 197, 198, 199,200, 201, 202, 203, 204, 205, 277, 278, 279, 280, 281, 282, 283, 284,285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 206, 207, 208, 209,210, 211, 212, 213, 214, 215, 216, 217, 218, 295, 296, 297, 298, 299,300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 219,220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 313, 314,315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328,329, 330, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243,244 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343,344, 345, 346, 347, 348, 349, 350

TABLE 31 Cna_B domain antigens comprising SEQ ID NO: 85 (S. equi proteinancillary protein SEQ0935 undefined product 914186:916159 forwardMW:73872 67; SEQ ID NO: 87) number of additional contiguous amino acidsof SEQ ID NO: 87 at N terminus of number of additional contiguous aminoacids of SEQ ID NO: 85 SEQ ID NO: 87 at C terminus of SEQ ID NO: 850-539, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 0-55, e.g., 0, 1,2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 16, 17,18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 52, 53, 54, 55, 56,57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74,75, 76, 77, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,96, 97, 98, 99, 100, 101, 102, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116,117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130,131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144,145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158,159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172,173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186,187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200,201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214,215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228,229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242,243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254, 255, 256,257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268, 269, 270,271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284,285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298,299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312,313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326,327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340,341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354,355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368,369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382,383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396,397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410,411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424,425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438,439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452,453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466,467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480,481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494,495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508,509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522,523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536,537, 538, 539

TABLE 32 Cna_B domain antigens comprising SEQ ID NO: 86 (S. equi proteinBKB SEQ0936 undefined product 916183:917625 forward MW:51902 46, 3; SEQID NO: 88) number of additional contiguous amino acids of SEQ ID NO: 88at N terminus number of additional contiguous amino acids of of SEQ IDNO: 86 SEQ ID NO: 88 at C terminus of SEQ ID NO: 86 0-336, e.g., 0, 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23,24, 0-74, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40,41, 42, 43, 44, 45, 46, 47, 48, 49, 17, 18, 19, 20, 21, 22, 23, 24, 25,26, 27, 28, 29, 30, 31, 32, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60,61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 33, 34, 35, 36,37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 75, 76, 77, 78, 79, 80,81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98,99, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74 118, 119, 120,121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134,135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148,149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162,163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176,177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190,191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204,205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218,219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232,233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246,247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260,261, 262, 263, 264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274,275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288,289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302,303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316,317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330,331, 332, 333, 334, 335, 336

TABLE 33 Cna_B domain antigens comprising SEQ ID NO: 122 (S. pyogenesprotein F2, Spy0119; SEQ ID NO: 121) number of additional contiguousamino acids of SEQ ID NO: 121 at N terminus of SEQ ID NO: 122 number ofadditional contiguous amino acids of SEQ ID NO: 121 at C terminus of SEQID NO: 122 0-59, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 0-1030,e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 12, 13, 14, 15, 16, 17, 18,19, 20, 21, 22, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43,44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 23, 24,25, 26, 27, 28, 29, 30, 31, 32, 33, 60, 61, 62, 63, 64, 65, 66, 67, 68,69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86,87, 88, 89, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 90, 91, 92, 93,94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108,109, 110, 111, 112, 113, 114, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54,55, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127,128, 129, 130, 131, 132, 133, 134, 135, 136, 56, 57, 58, 59 137, 138,139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152,153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166,167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180,181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194,195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208,209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222,223, 224, 225, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236,237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250,251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264,265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278,279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292,293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306,307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320,321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334,335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348,349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362,363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376,377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390,391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404,405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418,419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432,433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446,447, 448, 449, 450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 460,461, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474,475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488,489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502,503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516,517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530,531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544,545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558,559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572,573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586,587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600,601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614,615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628,629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642,643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656,657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670,671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684,685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698,699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712,713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726,727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740,741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754,755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768,769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782,783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796,797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810,811, 812, 813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824,825, 826, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838,839, 840, 841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852,853, 854, 855, 856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866,867, 868, 869, 870, 871, 872, 873, 874, 875, 876, 877, 878, 879, 880,881, 882, 883, 884, 885, 886, 887, 888, 889, 890, 891, 892, 893, 894,895, 896, 897, 898, 899, 900, 901, 902, 903, 904, 905, 906, 907, 908,909, 910, 911, 912, 913, 914, 915, 916, 917, 918, 919, 920, 921, 922,923, 924, 925, 926, 927, 928, 929, 930, 931, 932, 933, 934, 935, 936,937, 938, 939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950,951, 952, 953, 954, 955, 956, 957, 958, 959, 960, 961, 962, 963, 964,965, 966, 967, 968, 969, 970, 971, 972, 973, 974, 975, 976, 977, 978,979, 980, 981, 982, 983, 984, 985, 986, 987, 988, 989, 990, 991, 992,993, 994, 995, 996, 997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005,1006, 1007, 1008, 1009, 1010, 1011, 1012, 1013,

TABLE 34 Cna_B domain antigens comprising SEQ ID NO: 123 (S. pyogenesprotein F2, Spy0119; SEQ ID NO: 121) number of additional contiguousamino acids of SEQ ID NO: 121 at N number of additional contiguous aminoacids of SEQ ID terminus of SEQ ID NO: 123 NO: 121 at C terminus of SEQID NO: 123 0-524, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 0-561, e.g., 0, 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32,33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 16, 17, 18, 19, 20,21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 46, 47, 48, 49, 50, 51, 52,53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 69, 70, 71, 72,73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90,91, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 92,93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108,109, 110, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78,79, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123,124, 125, 126, 127, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92,93, 94, 95, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139,140, 141, 142, 143, 144, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155,156, 157, 158, 159, 160, 161, 109, 110, 111, 112, 113, 114, 115, 116,117, 118, 119, 120, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171,172, 173, 174, 175, 176, 177, 178, 121, 122, 123, 124, 125, 126, 127,128, 129, 130, 131,132, 179, 180, 181, 182, 183, 184, 185, 186, 187,188, 189, 190, 191, 192, 193, 194, 195, 133, 134, 135, 136, 137, 138,139, 140, 141, 142, 143, 144, 196, 197, 198, 199, 200, 201, 202, 203,204, 205, 206, 207, 208, 209, 210, 211, 212, 145, 146, 147, 148, 149,150, 151, 152, 153, 154, 155, 156, 213, 214, 215, 216, 217, 218, 219,220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 157, 158, 159, 160,161, 162, 163, 164, 165, 166, 167, 168, 230, 231, 232, 233, 234, 235,236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246, 169, 170, 171,172, 173, 174, 175, 176, 177, 178, 179, 180, 247, 248, 249, 250, 251,252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 181, 182,183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 264, 265, 266, 267,268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 193,194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 281, 282, 283,284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297,205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 298, 299,300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313,314, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 315,316, 317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329,330, 331, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240,332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345,346, 347, 348, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251,252, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361,362, 363, 364, 365, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262,263, 264, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377,378, 379, 380, 381, 382, 265, 266, 267, 268, 269, 270, 271, 272, 273,274, 275, 276, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393,394, 395, 396, 397, 398, 399, 277, 278, 279, 280, 281, 282, 283, 284,285, 286, 287, 288, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409,410, 411, 412, 413, 414, 415, 416, 289, 290, 291, 292, 293, 294, 295,296, 297, 298, 299, 300, 417, 418, 419, 420, 421, 422, 423, 424, 425,426, 427, 428, 429, 430, 431, 432, 433, 301, 302, 303, 304, 305, 306,307, 308, 309, 310, 311, 312, 434, 435, 436, 437, 438, 439, 440, 441,442, 443, 444, 445, 446, 447, 448, 449, 450, 313, 314, 315, 316, 317,318, 319, 320, 321, 322, 323, 324, 451, 452, 453, 454, 455, 456, 457,458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 325, 326,327, 328,329, 330, 331, 332, 333, 334, 335, 336, 468, 469, 470, 471, 472, 473,474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484, 337, 338,339,340, 341, 342, 343, 344, 345, 346, 347, 348, 485, 486, 487, 488,489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 349,350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 502, 503, 504,505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518,361, 362, 363, 364, 365,366, 367, 368, 369, 370, 371, 372, 519, 520,521, 522, 523, 524 373, 374, 375, 376, 377, 378, 379, 380, 381, 382,383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396,397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410,411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424,425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438,439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452,453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466,467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480,481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494,495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508,509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522,523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536,537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550,551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561

TABLE 35 Cna_B domain antigens comprising SEQ ID NO: 124 (S. pyogenesprotein F2, Spy0119; SEQ ID NO: 121) number of additional contiguousamino acids of SEQ ID NO: 121 at N number of additional contiguous aminoacids of terminus of SEQ ID NO: 124 SEQ ID NO: 121 at C terminus of SEQID NO: 124 0-637, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 0-451, e.g., 0, 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34,35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 50, 51, 52, 53, 54, 55, 56,57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74,28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 75, 76, 77, 78,79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96,97, 98, 99, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69,118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131,132, 133, 134, 135, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82,83, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148,149, 150, 151, 152, 153, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,96, 97, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166,167, 168, 169, 170, 171, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107,108, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 188, 189, 109, 110, 111, 112, 113, 114, 115, 116, 117,118, 119, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201,202, 203, 204, 205, 206, 207, 120, 121, 122, 123, 124, 125, 126, 127,128, 129, 130, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218,219, 220, 221, 222, 223, 224, 225, 131, 132, 133, 134, 135, 136, 137,138, 139, 140, 141, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235,236, 237, 238, 239, 240, 241, 242, 243, 142, 143, 144, 145, 146, 147,148, 149, 150, 151, 152, 244, 245, 246, 247, 248, 249, 250, 251, 252,253, 254, 255, 256, 257, 258, 259, 260, 261, 153, 154, 155, 156, 157,158, 159, 160, 161, 162, 163, 262, 263, 264, 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 164, 165, 166, 167,168, 169, 170, 171, 172, 173, 174, 280, 281, 282, 283, 284, 285, 286,287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 175, 176, 177,178, 179, 180, 181, 182, 183, 184, 185, 298, 299, 300, 301, 302, 303,304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 186, 187,188, 189, 190, 191, 192, 193, 194, 195, 196, 316, 317, 318, 319, 320,321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 197,198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 334, 335, 336, 337,338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351,208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 352, 353, 354,355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368,369, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 370, 371,372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385,386, 387, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 388,389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402,403, 404, 405, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251,406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419,420, 421, 422, 423, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261,262, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436,437, 438, 439, 440, 441, 263, 264, 265, 266, 267, 268, 269, 270, 271,272, 273, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453,454, 455, 456, 457, 458, 459, 274, 275, 276, 277, 278, 279, 280, 281,282, 283, 284, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470,471, 472, 473, 474, 475, 476, 477, 285, 286, 287, 288, 289, 290, 291,292, 293, 294, 295, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487,488, 489, 490, 491, 492, 493, 494, 495, 296, 297, 298, 299, 300, 301,302, 303, 304, 305, 306, 496, 497, 498, 499, 500, 501, 502, 503, 504,505, 506, 507, 508, 509, 510, 511, 512, 513, 307, 308, 309, 310, 311,312, 313, 314, 315, 316, 317, 514, 515, 516, 517, 518, 519, 520, 521,522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 318, 319, 320, 321,322, 323, 324, 325, 326, 327, 328, 532, 533, 534, 535, 536, 537, 538,539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 329, 330, 331,332, 333, 334, 335, 336, 337, 338, 339, 550, 551, 552, 553, 554, 555,556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 340, 341,342, 343, 344, 345, 346, 347, 348, 349, 350, 568, 569, 570, 571, 572,573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 351,352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 586, 587, 588, 589,590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603,362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 604, 605, 606,607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620,621, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 622, 623,624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397,398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411,412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425,426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439,440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451

TABLE 36 Cna_B domain antigens comprising SEQ ID NO: 125 (S. pyogenesprotein F2, Spy0119; SEQ ID NO: 121) number of additional contiguousamino acids of SEQ ID NO: 121 at N number of additional contiguous aminoacids of terminus of SEQ ID NO: 125 SEQ ID NO: 121 at C terminus of SEQID NO: 125 0-759, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 0-328, e.g., 0, 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34,35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 50, 51, 52, 53, 54, 55, 56,57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74,28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 75, 76, 77, 78,79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96,97, 98, 99, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69,118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131,132, 133, 134, 135, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82,83, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148,149, 150, 151, 152, 153, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95,96, 97, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166,167, 168, 169, 170, 171, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107,108, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 188, 189, 109, 110, 111, 112, 113, 114, 115, 116, 117,118, 119, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201,202, 203, 204, 205, 206, 207, 120, 121, 122, 123, 124, 125, 126, 127,128, 129, 130, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218,219, 220, 221, 222, 223, 224, 225, 131, 132, 133, 134, 135, 136, 137,138, 139, 140, 141, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235,236, 237, 238, 239, 240, 241, 242, 243, 142, 143, 144, 145, 146, 147,148, 149, 150, 151, 152, 244, 245, 246, 247, 248, 249, 250, 251, 252,253, 254, 255, 256, 257, 258, 259, 260, 261, 153, 154, 155, 156, 157,158, 159, 160, 161, 162, 163, 262, 263, 264, 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 164, 165, 166, 167,168, 169, 170, 171, 172, 173, 174, 280, 281, 282, 283, 284, 285, 286,287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 175, 176, 177,178, 179, 180, 181, 182, 183, 184, 185, 298, 299, 300, 301, 302, 303,304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 186, 187,188, 189, 190, 191, 192, 193, 194, 195, 196, 316, 317, 318, 319, 320,321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 197,198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 334, 335, 336, 337,338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351,208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 352, 353, 354,355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368,369, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229, 370, 371,372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385,386, 387, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 388,389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402,403, 404, 405, 241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251,406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419,420, 421, 422, 423, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261,262, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436,437, 438, 439, 440, 441, 263, 264, 265, 266, 267, 268, 269, 270, 271,272, 273, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453,454, 455, 456, 457, 458, 459, 274, 275, 276, 277, 278, 279, 280, 281,282, 283, 284, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470,471, 472, 473, 474, 475, 476, 477, 285, 286, 287, 288, 289, 290, 291,292, 293, 294, 295, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487,488, 489, 490, 491, 492, 493, 494, 495, 296, 297, 298, 299, 300, 301,302, 303, 304, 305, 306, 496, 497, 498, 499, 500, 501, 502, 503, 504,505, 506, 507, 508, 509, 510, 511, 512, 513, 307, 308, 309, 310, 311,312, 313, 314, 315, 316, 317, 514, 515, 516, 517, 518, 519, 520, 521,522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 318, 319, 320, 321,322, 323, 324, 325, 326, 327, 328 532, 533, 534, 535, 536, 537, 538,539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552,553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566,567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580,581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594,595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608,609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622,623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636,637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650,651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664,665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678,679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692,693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706,707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720,721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734,735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748,749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759

TABLE 37 Cna_B domain antigens comprising SEQ ID NO: 126 (S. pyogenesprotein F2, Spy0119; SEQ ID NO: 121) number of additional contiguousamino acids of SEQ ID NO: 121 at N number of additional contiguous aminoacids of terminus of SEQ ID NO: 126 SEQ ID NO: 121 at C terminus of SEQID NO: 126 0-904, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 0-188, e.g., 0, 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35,36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 13, 14, 15, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 50, 51, 52, 53, 54, 55, 56, 57, 58,59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 26, 27,28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 75, 76, 77, 78, 79, 80, 81,82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99,39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 100, 101, 102, 103,104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117,52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 118, 119, 120, 121,122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135,65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 136, 137, 138, 139,140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153,78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 154, 155, 156, 157,158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171,91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 172, 173, 174, 175,176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189,109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 190, 191, 192, 193,194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207,119, 120, 103, 104, 105, 106, 107, 108, 121, 122, 208, 209, 210, 211,212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225,123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 226, 227, 228, 229,230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243,133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 244, 245, 246, 247,248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261,143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 262, 263, 264, 265,266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279,153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 280, 281, 282, 283,284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297,163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 298, 299, 300, 301,302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315,173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 316, 317, 318, 319,320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333,183, 184, 185, 186, 187, 188 334, 335, 336, 337, 338, 339, 340, 341,342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355,356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369,370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383,384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397,398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411,412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425,426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439,440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453,454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467,468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481,482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495,496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509,510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523,524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537,538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551,552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565,566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579,580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593,594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607,608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621,622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635,636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649,650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663,664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677,678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691,692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705,706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719,720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733,734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747,748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761,762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775,776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789,790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803,804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817,818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828, 829, 830, 831,832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845,846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859,860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870, 871, 872, 873,874, 875, 876, 877, 878, 879, 880, 881, 882, 883, 884, 885, 886, 887,888, 889, 890, 891, 892, 893, 894, 895, 896, 897, 898, 899, 900, 901,902, 903, 904

TABLE 43 Cna_B domain antigens comprising SEQ ID NO: 134 (Cna_B domainof S. aureus SdrD protein, SEQ ID NO: 132) number of additionalcontiguous amino acids of SEQ ID NO: 132 at N number of additionalcontiguous amino acids of terminus of SEQ ID NO: 134 SEQ ID NO: 132 at Cterminus of SEQ ID NO: 134 0-591, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 0-683, e.g., 0, 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 23, 24, 25, 26, 27, 28,29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 46, 47, 48,49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66,67, 68, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47,69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86,87, 88, 89, 90, 91, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60,61, 62, 63, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104,105, 106, 107, 108, 109, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75,76, 77, 78, 79, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120,121, 122, 123, 124, 125, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91,92, 93, 94, 95, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136,137, 138, 139, 140, 141, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105,106, 107, 108, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152,153, 154, 155, 156, 157, 109, 110, 111, 112, 113, 114, 115, 116, 117,118, 119, 120, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168,169, 170, 171, 172, 173, 121, 122, 123, 124, 125, 126, 127, 128, 129,130, 131, 132, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 188, 189, 133, 134, 135, 136, 137, 138, 139, 140, 141,142, 143, 144, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200,201, 202, 203, 204, 205, 145, 146, 147, 148, 149, 150, 151, 152, 153,154, 155, 156, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216,217, 218, 219, 220, 221, 157, 158, 159, 160, 161, 162, 163, 164, 165,166, 167, 168, 222, 223, 224, 225, 226, 227, 228, 229, 230, 231, 232,233, 234, 235, 236, 237, 169, 170, 171, 172, 173, 174, 175, 176, 177,178, 179, 180, 238, 239, 240, 241, 242, 243, 244, 245, 246, 247, 248,249, 250, 251, 252, 253, 181, 182, 183, 184, 185, 186, 187, 188, 189,190, 191, 192, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264,265, 266, 267, 268, 269, 193, 194, 195, 196, 197, 198, 199, 200, 201,202, 203, 204, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280,281, 282, 283, 284, 285, 205, 206, 207, 208, 209, 210, 211, 212, 213,214, 215, 216, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296,297, 298, 299, 300, 301, 217, 218, 219, 220, 221, 222, 223, 224, 225,226, 227, 228, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312,313, 314, 315, 316, 317, 229, 230, 231, 232, 233, 234, 235, 236, 237,238, 239, 240, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328,329, 330, 331, 332, 333, 241, 242, 243, 244, 245, 246, 247, 248, 249,250, 251, 252, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344,345, 346, 347, 348, 349, 253, 254, 255, 256, 257, 258, 259, 260, 261,262, 263, 264, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360,361, 362, 363, 364, 365, 265, 266, 267, 268, 269, 270, 271, 272, 273,274, 275, 276, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376,377, 378, 379, 380, 381, 277, 278, 279, 280, 281, 282, 283, 284, 285,286, 287, 288, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392,393, 394, 395, 396, 397, 289, 290, 291, 292, 293, 294, 295, 296, 297,298, 299, 300, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408,409, 410, 411, 412, 413, 301, 302, 303, 304, 305, 306, 307, 308, 309,310, 311, 312, 414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424,425, 426, 427, 428, 429, 313, 314, 315, 316, 317, 318, 319, 320, 321,322, 323, 324, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440,441, 442, 443, 444, 445, 325, 326, 327, 328, 329, 330, 331, 332, 333,334, 335, 336, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456,457, 458, 459, 460, 461, 337, 338, 339, 340, 341, 342, 343, 344, 345,346, 347, 348, 462, 463, 464, 465, 466, 467, 468, 469, 470, 471, 472,473, 474, 475, 476, 477, 349, 350, 351, 352, 353, 354, 355, 356, 357,358, 359, 360, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488,489, 490, 491, 492, 493, 361, 362, 363, 364, 365, 366, 367, 368, 369,370, 371, 372, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504,505, 506, 507, 508, 509, 373, 374, 375, 376, 377, 378, 379, 380, 381,382, 383, 384, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520,521, 522, 523, 524, 525, 385, 386, 387, 388, 389, 390, 391, 392, 393,394, 395, 396, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536,537, 538, 539, 540, 541, 397, 398, 399, 400, 401, 402, 403, 404, 405,406, 407, 408, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552,553, 554, 555, 556, 557, 409, 410, 411, 412, 413, 414, 415, 416, 417,418, 419, 420, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568,569, 570, 571, 572, 573, 421, 422, 423, 424, 425, 426, 427, 428, 429,430, 431, 432, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584,585, 586, 587, 588, 589, 433, 434, 435, 436, 437, 438, 439, 440, 441,442, 443, 444, 590, 591 445, 446, 447, 448, 449, 450, 451, 452, 453,454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467,468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481,482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495,496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509,510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523,524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537,538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551,552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565,566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579,580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593,594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607,608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621,622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635,636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649,650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663,664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677,678, 679, 680, 681, 682, 683

TABLE 44 Cna_B domain antigens comprising SEQ ID NO: 135 (Cna_B domainof S. aureus SdrD protein, SEQ ID NO: 132) number of additionalcontiguous amino acids of SEQ ID NO: 132 at N number of additionalcontiguous amino acids of terminus of SEQ ID NO: 135 SEQ ID NO: 132 at Cterminus of SEQ ID NO: 135 0-703, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 0-572, e.g., 0, 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 23, 24, 25, 26, 27, 28,29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 16,17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 46, 47, 48,49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66,67, 68, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47,69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86,87, 88, 89, 90, 91, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60,61, 62, 63, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104,105, 106, 107, 108, 109, 110, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73,74, 75, 76, 77, 78, 79, 111, 112, 113, 114, 115, 116, 117, 118, 119,120, 121, 122, 123, 124, 125, 126, 127, 80, 81, 82, 83, 84, 85, 86, 87,88, 89, 90, 91, 92, 93, 94, 95, 128, 129, 130, 131, 132, 133, 134, 135,136, 137, 138, 139, 140, 141, 142, 143, 144, 96, 97, 98, 99, 100, 101,102, 103, 104, 105, 106, 107, 108, 145, 146, 147, 148, 149, 150, 151,152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 109, 110, 111, 112,113, 114, 115, 116, 117, 118, 119, 120, 162, 163, 164, 165, 166, 167,168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 121, 122, 123,124, 125, 126, 127, 128, 129, 130, 131, 132, 179, 180, 181, 182, 183,184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 133, 134,135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 196, 197, 198, 199,200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 145,146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 213, 214, 215,216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 229,157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 230, 231,232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245,246, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 247,248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261,262, 263, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192,264, 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277,278, 279, 280, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203,204, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293,294, 295, 296, 297, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214,215, 216, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309,310, 311, 312, 313, 314, 217, 218, 219, 220, 221, 222, 223, 224, 225,226, 227, 228, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325,326, 327, 328, 329, 330, 331, 229, 230, 231, 232, 233, 234, 235, 236,237, 238, 239, 240, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341,342, 343, 344, 345, 346, 347, 348, 241, 242, 243, 244, 245, 246, 247,248, 249, 250, 251, 252, 349, 350, 351, 352, 353, 354, 355, 356, 357,358, 359, 360, 361, 362, 363, 364, 365, 253, 254, 255, 256, 257, 258,259, 260, 261, 262, 263, 264, 366, 367, 368, 369, 370, 371, 372, 373,374, 375, 376, 377, 378, 379, 380, 381, 382, 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 383, 384, 385, 386, 387, 388, 389,390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 277, 278, 279, 280,281, 282, 283, 284, 285, 286, 287, 288, 400, 401, 402, 403, 404, 405,406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 289, 290, 291,292, 293, 294, 295, 296, 297, 298, 299, 300, 417, 418, 419, 420, 421,422, 423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 301, 302,303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 434, 435, 436, 437,438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 313,314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 451, 452, 453,454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467,325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 468, 469,470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483,484, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 485,486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499,500, 501, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360,502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515,516, 517, 518, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371,372, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531,532, 533, 534, 535, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382,383, 384, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547,548, 549, 550, 551, 552, 385, 386, 387, 388, 389, 390, 391, 392, 393,394, 395, 396, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563,564, 565, 566, 567, 568, 569, 397, 398, 399, 400, 401, 402, 403, 404,405, 406, 407, 408, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579,580, 581, 582, 583, 584, 585, 586, 409, 410, 411, 412, 413, 414, 415,416, 417, 418, 419, 420, 587, 588, 589, 590, 591, 592, 593, 594, 595,596, 597, 598, 599, 600, 601, 602, 603, 421, 422, 423, 424, 425, 426,427, 428, 429, 430, 431, 432, 604, 605, 606, 607, 608, 609, 610, 611,612, 613, 614, 615, 616, 617, 618, 619, 620, 433, 434, 435, 436, 437,438, 439, 440, 441, 442, 443, 444, 621, 622, 623, 624, 625, 626, 627,628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 445, 446, 447, 448,449, 450, 451, 452, 453, 454, 455, 456, 638, 639, 640, 641, 642, 643,644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 457, 458, 459,460, 461, 462, 463, 464, 465, 466, 467, 468, 655, 656, 657, 658, 659,660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 469, 470,471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 672, 673, 674, 675,676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 481,482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492, 689, 690, 691,692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703 493, 494,495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508,509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522,523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536,537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550,551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564,565, 566, 567, 568, 569, 570, 571, 572

TABLE 45 Cna_B domain antigens comprising SEQ ID NO: 136 (Cna_B domainof S. aureus SdrD protein, SEQ ID NO: 132) number of additionalcontiguous amino acids of SEQ ID NO: 132 at N number of additionalcontiguous amino acids of terminus of SEQ ID NO: 136 SEQ ID NO: 132 at Cterminus of SEQ ID NO: 136 0-814, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 0-461, e.g.,0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,49, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 50, 51, 52,53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70,71, 72, 73, 74, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92,93, 94, 95, 96, 97, 98, 99, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,53, 54, 55, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111,112, 113, 114, 115, 116, 117, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,129, 130, 131, 132, 133, 134, 135, 70, 71, 72, 73, 74, 75, 76, 77, 78,79, 80, 81, 82, 83, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145,146, 147, 148, 149, 150, 151, 152, 153, 84, 85, 86, 87, 88, 89, 90, 91,92, 93, 94, 95, 96, 97, 154, 155, 156, 157, 158, 159, 160, 161, 162,163, 164, 165, 166, 167, 168, 169, 170, 171, 98, 99, 100, 101, 102, 103,104, 105, 106, 107, 108, 172, 173, 174, 175, 176, 177, 178, 179, 180,181, 182, 183, 184, 185, 186, 187, 188, 189, 109, 110, 111, 112, 113,114, 115, 116, 117, 118, 119, 190, 191, 192, 193, 194, 195, 196, 197,198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 120, 121, 122, 123,124, 125, 126, 127, 128, 129, 130, 208, 209, 210, 211, 212, 213, 214,215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 131, 132, 133,134, 135, 136, 137, 138, 139, 140, 141, 226, 227, 228, 229, 230, 231,232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 142, 143,144, 145, 146, 147, 148, 149, 150, 151, 152, 244, 245, 246, 247, 248,249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 153,154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 262, 263, 264, 265,266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279,164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 280, 281, 282,283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296,297, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 298, 299,300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313,314, 315, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 316,317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330,331, 332, 333, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207,334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347,348, 349, 350, 351, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217,218, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364,365, 366, 367, 368, 369, 219, 220, 221, 222, 223, 224, 225, 226, 227,228, 229, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381,382, 383, 384, 385, 386, 387, 230, 231, 232, 233, 234, 235, 236, 237,238, 239, 240, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398,399, 400, 401, 402, 403, 404, 405, 241, 242, 243, 244, 245, 246, 247,248, 249, 250, 251, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415,416, 417, 418, 419, 420, 421, 422, 423, 252, 253, 254, 255, 256, 257,258, 259, 260, 261, 262, 424, 425, 426, 427, 428, 429, 430, 431, 432,433, 434, 435, 436, 437, 438, 439, 440, 441, 263, 264, 265, 266, 267,268, 269, 270, 271, 272, 273, 442, 443, 444, 445, 446, 447, 448, 449,450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 274, 275, 276, 277,278, 279, 280, 281, 282, 283, 284, 460, 461, 462, 463, 464, 465, 466,467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 285, 286, 287,288, 289, 290, 291, 292, 293, 294, 295, 478, 479, 480, 481, 482, 483,484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 296, 297,298, 299, 300, 301, 302, 303, 304, 305, 306, 496, 497, 498, 499, 500,501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 307,308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 514, 515, 516, 517,518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531,318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 532, 533, 534,535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548,549, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 550, 551,552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565,566, 567, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 568,569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582,583, 584, 585, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361,586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599,600, 601, 602, 603, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371,372, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616,617, 618, 619, 620, 621, 373, 374, 375, 376, 377, 378, 379, 380, 381,382, 383, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633,634, 635, 636, 637, 638, 639, 384, 385, 386, 387, 388, 389, 390, 391,392, 393, 394, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650,651, 652, 653, 654, 655, 656, 657, 395, 396, 397, 398, 399, 400, 401,402, 403, 404, 405, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667,668, 669, 670, 671, 672, 673, 674, 675, 406, 407, 408, 409, 410, 411,412, 413, 414, 415, 416, 676, 677, 678, 679, 680, 681, 682, 683, 684,685, 686, 687, 688, 689, 690, 691, 692, 693, 417, 418, 419, 420, 421,422, 423, 424, 425, 426, 427, 694, 695, 696, 697, 698, 699, 700, 701,702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 428, 429, 430, 431,432, 433, 434, 435, 436, 437, 438, 712, 713, 714, 715, 716, 717, 718,719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 439, 440, 441,442, 443, 444, 445, 446, 447, 448, 449, 730, 731, 732, 733, 734, 735,736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 450, 451,452, 453, 454, 455, 456, 457, 458, 459, 460, 748, 749, 750, 751, 752,753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 461766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779,780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793,794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807,808, 809, 810, 811, 812, 813, 814

TABLE 46 Cna_B domain antigens comprising SEQ ID NO: 137 (Cna_B domainof S. aureus SdrD protein, SEQ ID NO: 132) number of additionalcontiguous amino acids of SEQ ID NO: 132 at N number of additionalcontiguous amino acids of terminus of SEQ ID NO: 137 SEQ ID NO: 132 at Cterminus of SEQ ID NO: 137 0-924, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 0-351, e.g.,0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,49, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 50, 51, 52,53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70,71, 72, 73, 74, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92,93, 94, 95, 96, 97, 98, 99, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,53, 54, 55, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111,112, 113, 114, 115, 116, 117, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,129, 130, 131, 132, 133, 134, 135, 70, 71, 72, 73, 74, 75, 76, 77, 78,79, 80, 81, 82, 83, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145,146, 147, 148, 149, 150, 151, 152, 153, 84, 85, 86, 87, 88, 89, 90, 91,92, 93, 94, 95, 96, 97, 154, 155, 156, 157, 158, 159, 160, 161, 162,163, 164, 165, 166, 167, 168, 169, 170, 171, 98, 99, 100, 101, 102, 103,104, 105, 106, 107, 108, 172, 173, 174, 175, 176, 177, 178, 179, 180,181, 182, 183, 184, 185, 186, 187, 188, 189, 109, 110, 111, 112, 113,114, 115, 116, 117, 118, 119, 190, 191, 192, 193, 194, 195, 196, 197,198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 120, 121, 122, 123,124, 125, 126, 127, 128, 129, 130, 208, 209, 210, 211, 212, 213, 214,215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 131, 132, 133,134, 135, 136, 137, 138, 139, 140, 141, 226, 227, 228, 229, 230, 231,232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 142, 143,144, 145, 146, 147, 148, 149, 150, 151, 152, 244, 245, 246, 247, 248,249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 153,154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 262, 263, 264, 265,266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279,164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 280, 281, 282,283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296,297, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 298, 299,300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313,314, 315, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 316,317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330,331, 332, 333, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207,334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347,348, 349, 350, 351, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217,218, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364,365, 366, 367, 368, 369, 219, 220, 221, 222, 223, 224, 225, 226, 227,228, 229, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381,382, 383, 384, 385, 386, 387, 230, 231, 232, 233, 234, 235, 236, 237,238, 239, 240, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398,399, 400, 401, 402, 403, 404, 405, 241, 242, 243, 244, 245, 246, 247,248, 249, 250, 251, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415,416, 417, 418, 419, 420, 421, 422, 423, 252, 253, 254, 255, 256, 257,258, 259, 260, 261, 262, 424, 425, 426, 427, 428, 429, 430, 431, 432,433, 434, 435, 436, 437, 438, 439, 440, 441, 263, 264, 265, 266, 267,268, 269, 270, 271, 272, 273, 442, 443, 444, 445, 446, 447, 448, 449,450, 451, 452, 453, 454, 455, 456, 457, 458, 459, 274, 275, 276, 277,278, 279, 280, 281, 282, 283, 284, 460, 461, 462, 463, 464, 465, 466,467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 285, 286, 287,288, 289, 290, 291, 292, 293, 294, 295, 478, 479, 480, 481, 482, 483,484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 296, 297,298, 299, 300, 301, 302, 303, 304, 305, 306, 496, 497, 498, 499, 500,501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 307,308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 514, 515, 516, 517,518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531,318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 532, 533, 534,535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548,549, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 550, 551,552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565,566, 567, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 568,569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582,583, 584, 585, 351 586, 587, 588, 589, 590, 591, 592, 593, 594, 595,596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609,610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623,624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637,638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651,652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665,666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679,680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693,694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707,708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721,722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735,736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749,750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763,764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777,778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791,792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805,806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819,820, 821, 822, 823, 824, 825, 826, 827, 828, 829, 830, 831, 832, 833,834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847,848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861,862, 863, 864, 865, 866, 867, 868, 869, 870, 871, 872, 873, 874, 875,876, 877, 878, 879, 880, 881, 882, 883, 884, 885, 886, 887, 888, 889,890, 891, 892, 893, 894, 895, 896, 897, 898, 899, 900, 901, 902, 903,904, 905, 906, 907, 908, 909, 910, 911, 912, 913, 914, 915, 916, 917,918, 919, 920, 921, 922, 923, 924

TABLE 47 Cna_B domain antigens comprising SEQ ID NO: 138 (Cna_B domainof S. aureus SdrD protein, SEQ ID NO: 132) number of additionalcontiguous amino acids of SEQ ID NO: 132 at N number of additionalcontiguous amino acids of terminus of SEQ ID NO: 138 SEQ ID NO: 132 at Cterminus of SEQ ID NO: 138 0-1035, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 0-241, e.g.,0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 25, 26, 27, 28, 29, 30, 31,32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 50, 51, 52, 53,54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71,72, 73, 74, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 75,76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93,94, 95, 96, 97, 98, 99, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,53, 54, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112,113, 114, 115, 116, 117, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66,67, 68, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130,131, 132, 133, 134, 135, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80,81, 82, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148,149, 150, 151, 152, 153, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94,95, 96, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166,167, 168, 169, 170, 171, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106,107, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 188, 189, 108, 109, 110, 111, 112, 113, 114, 115, 116,117, 118, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201,202, 203, 204, 205, 206, 207, 119, 120, 121, 122, 123, 124, 125, 126,127, 128, 129, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218,219, 220, 221, 222, 223, 224, 225, 130, 131, 132, 133, 134, 135, 136,137, 138, 139, 140, 226, 227, 228, 229, 230, 231, 232, 233, 234, 235,236, 237, 238, 239, 240, 241, 242, 243, 141, 142, 143, 144, 145, 146,147, 148, 149, 150, 151, 244, 245, 246, 247, 248, 249, 250, 251, 252,253, 254, 255, 256, 257, 258, 259, 260, 261, 152, 153, 154, 155, 156,157, 158, 159, 160, 161, 162, 262, 263, 264, 265, 266, 267, 268, 269,270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 163, 164, 165, 166,167, 168, 169, 170, 171, 172, 173, 280, 281, 282, 283, 284, 285, 286,287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 174, 175, 176,177, 178, 179, 180, 181, 182, 183, 184, 298, 299, 300, 301, 302, 303,304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 185, 186,187, 188, 189, 190, 191, 192, 193, 194, 195, 316, 317, 318, 319, 320,321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 196,197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 334, 335, 336, 337,338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351,207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 352, 353, 354,355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368,369, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227, 228, 370, 371,372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385,386, 387, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 388,389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402,403, 404, 405, 240, 241 406, 407, 408, 409, 410, 411, 412, 413, 414,415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428,429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442,443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455, 456,457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469, 470,471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483, 484,485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498,499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511, 512,513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526,527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540,541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554,555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568,569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582,583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596,597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610,611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624,625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638,639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652,653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666,667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680,681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694,695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708,709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722,723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736,737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750,751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764,765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778,779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792,793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806,807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 820,821, 822, 823, 824, 825, 826, 827, 828, 829, 830, 831, 832, 833, 834,835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 848,849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861, 862,863, 864, 865, 866, 867, 868, 869, 870, 871, 872, 873, 874, 875, 876,877, 878, 879, 880, 881, 882, 883, 884, 885, 886, 887, 888, 889, 890,891, 892, 893, 894, 895, 896, 897, 898, 899, 900, 901, 902, 903, 904,905, 906, 907, 908, 909, 910, 911, 912, 913, 914, 915, 916, 917, 918,919, 920, 921, 922, 923, 924, 925, 926, 927, 928, 929, 930, 931, 932,933, 934, 935, 936, 937, 938, 939, 940, 941, 942, 943, 944, 945, 946,947, 948, 949, 950, 951, 952, 953, 954, 955, 956, 957, 958, 959, 960,961, 962, 963, 964, 965, 966, 967, 968, 969, 970, 971, 972, 973, 974,975, 976, 977, 978, 979, 980, 981, 982, 983, 984, 985, 986, 987, 988,989, 990, 991, 992, 993, 994, 995, 996, 997, 998, 999, 1000, 1001, 1002,1003, 1004, 1005, 1006, 1007, 1008, 1009, 1010, 1011, 1012, 1013, 1014,1015, 1016, 1017, 1018, 1019, 1020, 1021, 1022, 1023, 1024, 1025, 1026,1027, 1028, 1029, 1030, 1031, 1032, 1033, 1034, 1035

TABLE 48 Cna_B domain antigens comprising SEQ ID NO: 139 (Cna_B domainsof S. aureus SdrD protein, SEQ ID NO: 132) number of additionalcontiguous amino acids of SEQ ID NO: 132 at N number of additionalcontiguous amino acids of terminus of SEQ ID NO: 139 SEQ ID NO: 132 at Cterminus of SEQ ID NO: 139 0-598, e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 0-225, e.g.,0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 25, 26, 27, 28, 29, 30,31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48,49, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 50, 51, 52,53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70,71, 72, 73, 74, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92,93, 94, 95, 96, 97, 98, 99, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,53, 54, 55, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111,112, 113, 114, 115, 116, 117, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,129, 130, 131, 132, 133, 134, 135, 70, 71, 72, 73, 74, 75, 76, 77, 78,79, 80, 81, 82, 83, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145,146, 147, 148, 149, 150, 151, 152, 153, 84, 85, 86, 87, 88, 89, 90, 91,92, 93, 94, 95, 96, 97, 154, 155, 156, 157, 158, 159, 160, 161, 162,163, 164, 165, 166, 167, 168, 169, 170, 171, 98, 99, 100, 101, 102, 103,104, 105, 106, 107, 108, 172, 173, 174, 175, 176, 177, 178, 179, 180,181, 182, 183, 184, 185, 186, 187, 188, 189, 109, 110, 111, 112, 113,114, 115, 116, 117, 118, 119, 190, 191, 192, 193, 194, 195, 196, 197,198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 120, 121, 122, 123,124, 125, 126, 127, 128, 129, 130, 208, 209, 210, 211, 212, 213, 214,215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 131, 132, 133,134, 135, 136, 137, 138, 139, 140, 141, 226, 227, 228, 229, 230, 231,232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 142, 143,144, 145, 146, 147, 148, 149, 150, 151, 152, 244, 245, 246, 247, 248,249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 153,154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 262, 263, 264, 265,266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279,164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 280, 281, 282,283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296,297, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 298, 299,300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, 313,314, 315, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 316,317, 318, 319, 320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330,331, 332, 333, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207,334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347,348, 349, 350, 351, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217,218, 352, 353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364,365, 366, 367, 368, 369, 219, 220, 221, 222, 223, 224, 225 370, 371,372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385,386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399,400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413,414, 415, 416, 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427,428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441,442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452, 453, 454, 455,456, 457, 458, 459, 460, 461, 462, 463, 464, 465, 466, 467, 468, 469,470, 471, 472, 473, 474, 475, 476, 477, 478, 479, 480, 481, 482, 483,484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497,498, 499, 500, 501, 502, 503, 504, 505, 506, 507, 508, 509, 510, 511,512, 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525,526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539,540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553,554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567,568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581,582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595,596, 597, 598

Nucleic Acid Molecules

The invention includes nucleic acid molecules which encode Cna_B domainantigens of the invention. The invention also includes nucleic acidmolecules comprising nucleotide sequences having at least 95% sequenceidentity to such molecules. Depending on the particular sequence, thedegree of sequence identity is preferably at least 95%, 96%, 97%, 98%,or 99%. Identity between nucleotide sequences is preferably determinedby the Smith-Waterman homology search algorithm as implemented in theMPSRCH program (Oxford Molecular), using an affine gap search withparameters gap open penalty=12 and gap extension penalty=1.

The invention also provides nucleic acid molecules which can hybridizeto these molecules. Hybridization reactions can be performed underconditions of different stringency. Conditions which increase stringencyof a hybridization reaction are widely known and published in the art.See, e.g., page 7.52 of Sambrook et al., Molecular Cloning: A LaboratoryManual, 1989. Examples of relevant conditions include (in order ofincreasing stringency): incubation temperatures of 25° C., 37° C., 50°C., 55° C., and 68° C.; buffer concentrations of 10×SSC, 6×SSC, 1×SSC,and 0.1×SSC (where SSC is 0.15 M NaCl and 15 mM citrate buffer) andtheir equivalents using other buffer systems; formamide concentrationsof 0%, 25%, 50%, and 75%; incubation times from 5 minutes to 24 hours;1, 2, or more washing steps; wash incubation times of 1, 2, or 15minutes; and wash solutions of 6×SSC, 1×SSC, 0.1×SSC, or de-ionizedwater. Hybridization techniques and their optimization are well known inthe art. See, e.g., Sambrook, 1989; Ausubel et al., eds., ShortProtocols in Molecular Biology, 4th ed., 1999; U.S. Pat. No. 5,707,829;Ausubel et al., eds., Current Protocols in Molecular Biology, Supplement30, 1987.

In some embodiments, nucleic acid molecules of the invention hybridizeto a target under low stringency conditions; in other embodiments,nucleic acid molecules of the invention hybridize under intermediatestringency conditions; in preferred embodiments, nucleic acid moleculesof the invention hybridize under high stringency conditions. An exampleof a low stringency hybridization condition is 50° C. and 10×SSC. Anexample of an intermediate stringency hybridization condition is 55° C.and 1×SSC. An example of a high stringency hybridization condition is68° C. and 0.1×SSC.

Production of Cna_B Domain Antigens

Recombinant Production

The redundancy of the genetic code is well-known. Thus, any nucleic acidmolecule (polynucleotide) which encodes a Cna_B domain antigen of theinvention can be used to produce that protein recombinantly. Nucleicacid molecules encoding a Cna_B domain-containing protein can beisolated from the appropriate bacterium (e.g., a streptococcal orstaphylococcal bacterium) using standard nucleic acid purificationtechniques or can be synthesized using an amplification technique, suchas the polymerase chain reaction (PCR), or using an automaticsynthesizer. See Caruthers et al., Nucl. Acids Res. Symp. Ser. 215 223,1980; Horn et al. Nucl. Acids Res. Symp. Ser. 225 232, 1980; Hunkapilleret al., Nature 310, 105-11, 1984; Grantham et al., Nucleic Acids Res. 9,r43-r74, 1981.

cDNA molecules can be made with standard molecular biology techniques,using mRNA as a template. cDNA molecules can thereafter be replicatedusing molecular biology techniques well known in the art. Anamplification technique, such as PCR, can be used to obtain additionalcopies of polynucleotides of the invention, using either genomic DNA orcDNA as a template.

If desired, polynucleotides can be engineered using methods generallyknown in the art to alter coding sequences for a variety of reasons,including but not limited to, alterations which modify the cloning,processing, and/or expression of a polypeptide or mRNA product. DNAshuffling by random fragmentation and PCR reassembly of gene fragmentsand synthetic oligonucleotides can be used to engineer the nucleotidesequences. For example, site directed mutagenesis can be used to insertnew restriction sites, alter glycosylation patterns, change codonpreference, produce splice variants, introduce mutations, and so forth.

Nucleic acid molecules can include a coding sequence for an N-terminalleader sequence (either the N-terminal leader sequence of a nativeprotein comprising a Cna_B or another N-terminal leader sequence ofchoice). In some embodiments, sequence modifications, such as theaddition of a purification tag sequence or codon optimization, are usedto facilitate expression. For example, an expressed protein can comprisea tag such as polyhistidine (HIS) or glutathione S-transferase (GST).Such tags can be used to facilitate purification, detection, andstability of the expressed protein. Codons preferred by a particularprokaryotic or eukaryotic host can be selected to increase the rate ofprotein expression or to produce an RNA transcript having desirableproperties, such as a half life which is longer than that of atranscript generated from the naturally occurring sequence. Thesemethods are well known in the art and are described in WO 05/032582.

Expression Vectors

A nucleic acid molecule which encodes a Cna_B domain antigen can beinserted into an expression vector which contains the necessary elementsfor the transcription and translation of the inserted coding sequence.Methods which are well known to those skilled in the art can be used toconstruct expression vectors containing coding sequences and appropriatetranscriptional and translational control elements. These methodsinclude in vitro recombinant DNA techniques, synthetic techniques, andin vivo genetic recombination.

Host Cells

Host cells for producing Cna_B domain antigens can be prokaryotic oreukaryotic. E. coli is a preferred host cell, but other suitable hostsinclude Lactococcus lactis, Lactococcus cremoris, Bacillus subtilis,Vibrio cholerae, Salmonella typhi, Salmonella typhimurium, Neisserialactamica, Neisseria cinerea, Mycobacteria (e.g., M. tuberculosis),yeasts, baculovirus, mammalian cells, etc.

A host cell strain can be chosen for its ability to modulate theexpression of the inserted sequences or to process the expressedpolypeptide in the desired fashion. Such modifications of thepolypeptide include, but are not limited to, acetylation, carboxylation,glycosylation, phosphorylation, lipidation, and acylation. Posttranslational processing which cleaves a “prepro” form of thepolypeptide also can be used to facilitate correct insertion, foldingand/or function. Different host cells which have specific cellularmachinery and characteristic mechanisms for post translationalactivities are available from the American Type Culture Collection(ATCC; 10801 University Boulevard, Manassas, Va. 20110-2209) and can bechosen to ensure the correct modification and processing of a foreignprotein. See WO 01/98340.

Expression constructs can be introduced into host cells usingwell-established techniques which include, but are not limited to,transferrin-polycation-mediated DNA transfer, transfection with naked orencapsulated nucleic acids, liposome-mediated cellular fusion,intracellular transportation of DNA-coated latex beads, protoplastfusion, viral infection, electroporation, “gene gun” methods, and DEAE-or calcium phosphate-mediated transfection.

Host cells transformed with expression vectors can be cultured underconditions suitable for the expression and recovery of the protein fromcell culture. The protein produced by a transformed cell can be secretedor contained intracellularly depending on the nucleotide sequence and/orthe expression vector used. Those of skill in the art understand thatexpression vectors can be designed to contain signal sequences whichdirect secretion of soluble polypeptides through a prokaryotic oreukaryotic cell membrane.

Purification

Signal export sequences can be included in a recombinantly producedCna_B domain antigen so that the antigen can be purified from cellculture medium using known methods. Alternatively, recombinantlyproduced Cna_B domain antigens of the invention can be isolated fromengineered host cells and separated from other components in the cell,such as proteins, carbohydrates, or lipids, using methods well-known inthe art. Such methods include, but are not limited to, size exclusionchromatography, ammonium sulfate fractionation, ion exchangechromatography, affinity chromatography, and preparative gelelectrophoresis. A preparation of purified Cna_B domain antigens is atleast 80% pure; preferably, the preparations are 90%, 95%, or 99% pure.Purity of the preparations can be assessed by any means known in theart, such as SDS-polyacrylamide gel electrophoresis. Where appropriate,Cna_B domain antigens can be solubilized, for example, with urea.

Chemical Synthesis

Cna_B domain antigens can be synthesized, for example, using solid phasetechniques.

See, e.g., Merrifield, J. Am. Chem. Soc. 85, 2149 54, 1963; Roberge etal., Science 269, 202 04, 1995. Protein synthesis can be performed usingmanual techniques or by automation. Automated synthesis can be achieved,for example, using Applied Biosystems 431A Peptide Synthesizer (PerkinElmer). Optionally, portions of a Cna_B domain antigen can besynthesized separately and combined using chemical methods to producethe complete molecule.

Pharmaceutical Compositions

The invention provides compositions for use as medicaments.Pharmaceutical compositions of the invention are useful for raising animmune response against gram positive bacteria, particularlystreptococcal or staphylococcal bacteria (e.g., S. agalactiae, S.pyogenes, S. pneumoniae, and/or S. aureus). In some embodiments thecompositions are useful for treating streptococcal and/or staphylococcalinfections as well as reducing the risk of such infections.

Pharmaceutical compositions of the invention comprise at least oneactive agent, which can be a Cna_B domain antigen as disclosed herein ora nucleic acid molecule encoding the Cna_B domain antigen. The diseasecan be, for example, bacteremia, meningitis, puerperal fever, scarletfever, erysipelas, pharyngitis, impetigo, necrotizing fasciitis,myositis, or toxic shock syndrome.

Compositions containing a Cna_B domain antigen or a nucleic acidmolecule encoding a Cna_B domain antigen are preferably immunogeniccompositions, and are more preferably vaccine compositions.Pharmaceutical compositions according to the invention can be eitherprophylactic or therapeutic, but will typically be prophylactic. Apharmaceutical composition is “prophylactic” if it reduces the risk of agram positive bacterial (e.g., streptococcal and/or staphylococcal)infection or reduces the severity of a gram positive bacterial (e.g.,streptococcal and/or staphylococcal) infection or a symptom of a grampositive bacterial (e.g., streptococcal and/or staphylococcal)infection. Accordingly, the invention includes methods for thetherapeutic or prophylactic treatment of a gram positive bacterial(e.g., streptococcal and/or staphylococcal) infection. Animals,preferably mammals, most preferably humans, can be treated. The methodsinvolve administering to the animal a therapeutic or prophylactic amountof an immunogenic composition of the invention.

The pH of such compositions typically is between 6 and 8, preferablyabout 7. The pH can be maintained by the use of a buffer. Thecomposition can be sterile and/or pyrogen-free. The composition can beisotonic with respect to human tissue (e.g., blood).

Some compositions of the invention comprise one or more Cna_B domainantigens as described herein. Other compositions of the inventioncomprise one or more nucleic acid molecules which encodes the antigensand, optionally, other antigens which can be included in the composition(see below). See, e.g., Robinson & Torres (1997) Seminars in Immunology9:271-283; Donnelly et al. (1997) Ann. Rev Immunol 15:617-648;Scott-Taylor & Dalgleish (2000) Expert Opin Investig Drugs 9:471-480;Apostolopoulos & Plebanski (2000) Curr Opin Mol Ther 2:441-447; Ilan(1999) Curr Opin Mol Ther 1:116-120; Dubensky et al. (2000) Mol Med6:723-732; Robinson & Pertmer (2000) Adv Virus Res 55:1-74; Donnelly etal. (2000) Am J Respir Crit. Care Med 162(4 Pt 2):5190-193; Davis (1999)Mt. Sinai J. Med. 66:84-90. Typically the nucleic acid molecule is a DNAmolecule, e.g., in the form of a plasmid. In some embodiments,compositions of the invention can comprise one or more Cna_B domainantigens and one or more nucleic acid molecules.

Additional Active Agents

In some embodiments, compositions of the invention can include one ormore additional active agents. Such agents include, but are not limitedto, (a) another Cna_B domain antigen of the invention, (b) a polypeptideantigen which is useful in a pediatric vaccine, (c) a polypeptideantigen which is useful in a vaccine for elderly or immunocompromisedindividuals, (d) a nucleic acid molecule encoding (a)-(c), an antibodywhich specifically binds to (a)-(c), and a GBS polysaccharide antigen asdefined below.

Antibodies

Cna_B domains of gram positive bacterial (e.g., streptococcal and/orstaphylococcal) proteins can be used to generate antibodies, preferablyprotective antibodies. “Antibody” as used herein includes, but is notlimited to, intact immunoglobulin molecules, as well as fragmentsthereof which are capable of binding a Cna_B domain. “Antibodies”therefore can include monoclonal antibodies, hybrid (chimeric) antibodymolecules (e.g., Winter et al., Nature 349, 293-99, 1991; U.S. Pat. No.4,816,567); F(ab′)2 and F(ab) fragments and Fv molecules; non-covalentheterodimers (e.g., Inbar et al., Proc. Natl. Acad. Sci. U.S.A. 69,2659-62, 1972; Ehrlich et al., Biochem 19, 4091-96, 1980); single-chainFv molecules (sFv) (e.g., Huston et al., Proc. Natl. Acad. Sci. U.S.A.85, 5897-83, 1988); dimeric and trimeric antibody fragment constructs;minibodies (e.g., Pack et al., Biochem 31, 1579-84, 1992; Cumber et al.,J. Immunology 149B, 120-26, 1992); humanized antibody molecules (e.g.,Riechmann et al., Nature 332, 323-27, 1988; Verhoeyan et al., Science239, 1534-36, 1988; and U.K. Patent Publication No. GB 2,276,169,published 21 Sep. 1994); and any functional fragments obtained from suchmolecules, as well as antibodies obtained through non-conventionalprocesses such as phage display.

An antibody binds specifically to a Cna_B domain according to theinvention if it provides a detection signal at least 5-, 10-, or 20-foldhigher than a detection signal provided with other proteins when used inan immunochemical assay. Preferably, an antibody that binds specificallyto a Cna_B domain can immunoprecipitate that a Cna_B domain antigen fromsolution. In some embodiments, antibodies which bind specifically to aCna_B domain induce opsonophagocytosis of GBS strain 515 by at least 30%(e.g., 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100%).

Additional Antigens

Compositions of the invention may be administered in conjunction withone or more antigens for use in therapeutic or prophylactic methods ofthe present invention. Preferred antigens include those listed below.Additionally, the compositions of the present invention may be used totreat or prevent infections caused by any of the below-listed pathogens.In addition to combination with the antigens described below, thecompositions of the invention may also be combined with an adjuvant asdescribed herein.

GBS Polysaccharide Antigen

In some embodiments compositions of the invention comprise a GBSpolysaccharide antigen. S. agalactiae GBS carbohydrate typicallyfeatures a branched structure with an L-rhamnopyranose (Rhap) backboneconsisting of alternating alpha-(1→2) and alpha-(1→3) links andD-N-acetylglucosamine (GlcpNAc) residues beta-(1→3)-connected toalternating rhamnose rings (Kreis et al., Int. J. Biol. Macromol. 17,117-30, 1995). GBS polysaccharide antigens useful in compositions of theinvention have the formula:

wherein R is a terminal reducing L-Rhamnose or D-GlcpNAc and n is anumber from about 3 to about 30.

The GBS polysaccharide antigen used according to the invention may be asubstantially full-length GBS carbohydrate, as found in nature, or itmay be shorter than the natural length. Full-length polysaccharides maybe depolymerized to give shorter fragments for use with the invention,e.g., by hydrolysis in mild acid, by heating, by sizing chromatography,etc. However, it is preferred to use saccharides of substantiallyfull-length. In particular, it is preferred to use saccharides with amolecular weight of about 10 kDa. Molecular masses can be measured bygel filtration relative to dextran standards.

The saccharide may be chemically modified relative to the GBScarbohydrate as found in nature. For example, the saccharide may be de Nacetylated (partially or fully), N propionated (partially or fully),etc. The effect of de acetylation etc., for example on immunogenicity,can be assessed by routine assays.

In some embodiments the GBS polysaccharide antigen is conjugated to acarrier, such as the mutated diphtheria toxin CRM197 and other carriersdescribed below.

Antigens for use with the invention include, but are not limited to, oneor more of the following antigens set forth below, or antigens derivedfrom one or more of the pathogens set forth below:

A. BACTERIAL ANTIGENS

Bacterial antigens suitable for use in the invention include proteins,polysaccharides, lipopolysaccharides, and outer membrane vesicles whichmay be isolated, purified or derived from a bacteria. In addition,bacterial antigens may include bacterial lysates and inactivatedbacteria formulations. Bacteria antigens may be produced by recombinantexpression. Bacterial antigens preferably include epitopes which areexposed on the surface of the bacteria during at least one stage of itslife cycle. Bacterial antigens are preferably conserved across multipleserotypes. Bacterial antigens include antigens derived from one or moreof the bacteria set forth below as well as the specific antigensexamples identified below.

Neisseria meningitides: Meningitides antigens may include proteins (suchas those identified in References 1-7), saccharides (including apolysaccharide, oligosaccharide or lipopolysaccharide), orouter-membrane vesicles (References 8, 9, 10, 11) purified or derivedfrom N. meningitides serogroup such as A, C, W135, Y, and/or B.Meningitides protein antigens may be selected from adhesions,autotransporters, toxins, Fe acquisition proteins, and membraneassociated proteins (preferably integral outer membrane protein).

Streptococcus pneumoniae: Streptococcus pneumoniae antigens may includea saccharide (including a polysaccharide or an oligosaccharide) and/orprotein from Streptococcus pneumoniae. Saccharide antigens may beselected from serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F,14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F. Protein antigens maybe selected from a protein identified in WO 98/18931, WO 98/18930, U.S.Pat. No. 6,699,703, U.S. Pat. No. 6,800,744, WO 97/43303, and WO97/37026. Streptococcus pneumoniae proteins may be selected from thePoly Histidine Triad family (PhtX), the Choline Binding Protein family(CbpX), CbpX truncates, LytX family, LytX truncates, CbpX truncate-LytXtruncate chimeric proteins, pneumolysin (Ply), PspA, PsaA, Sp128, Sp101,Sp130, Sp125 or Sp133.

Streptococcus pyogenes (Group A Streptococcus): Group A Streptococcusantigens may include a protein identified in WO 02/34771 or WO2005/032582 (including GAS 40), fusions of fragments of GAS M proteins(including those described in WO 02/094851, and Dale, Vaccine (1999)17:193-200, and Dale, Vaccine 14(10): 944-948), fibronectin bindingprotein (Sfb1), Streptococcal heme-associated protein (Shp), andStreptolysin S (SagA).

Moraxella catarrhalis: Moraxella antigens include antigens identified inWO 02/18595 and WO 99/58562, outer membrane protein antigens (HMW-OMP),C-antigen, and/or LPS.

Bordetella pertussis: Pertussis antigens include petussis holotoxin (PT)and filamentous haemagglutinin (FHA) from B. pertussis, optionally alsocombination with pertactin and/or agglutinogens 2 and 3 antigen.

Staphylococcus aureus: Staphylococcus aureus antigens include S. aureustype 5 and 8 capsular polysaccharides optionally conjugated to nontoxicrecombinant Pseudomonas aeruginosa exotoxin A, such as StaphVAX™, orantigens derived from surface proteins, invasins (leukocidin, kinases,hyaluronidase), surface factors that inhibit phagocytic engulfment(capsule, Protein A), carotenoids, catalase production, Protein A,coagulase, clotting factor, and/or membrane-damaging toxins (optionallydetoxified) that lyse eukaryotic cell membranes (hemolysins, leukotoxin,leukocidin).

Staphylococcus epidermis: S. epidermidis antigens includeslime-associated antigen (SAA).

Clostridium tetani (Tetanus): Tetanus antigens include tetanus toxoid(TT), preferably used as a carrier protein in conjunction/conjugatedwith the compositions of the present invention.

Cornynebacterium diphtheriae (Diphtheria): Diphtheria antigens includediphtheria toxin, preferably detoxified, such as CRM197. Additionallyantigens capable of modulating, inhibiting or associated with ADPribosylation are contemplated forcombination/co-administration/conjugation with the compositions of thepresent invention. The diphtheria toxoids may be used as carrierproteins.

Haemophilus influenzae B (Hib): Hib antigens include a Hib saccharideantigen.

Pseudomonas aeruginosa: Pseudomonas antigens include endotoxin A, Wzzprotein, P. aeruginosa LPS, more particularly LPS isolated from PAO1 (O5serotype), and/or Outer Membrane Proteins, including Outer MembraneProteins F (OprF) (Infect Immun. 2001 May; 69(5): 3510-3515).

Legionella pneumophila. Bacterial antigens may be derived fromLegionella pneumophila.

Streptococcus agalactiae (Group B Streptococcus): Group B Streptococcusantigens include a protein or saccharide antigen identified in WO02/34771, WO 03/093306, WO 04/041157, or WO 2005/002619 (includingproteins GBS 80, GBS 104, GBS 276 and GBS 322, and including saccharideantigens derived from serotypes Ia, Ib, Ia/c, II, III, IV, V, VI, VIIand VIII).

Neiserria gonorrhoeae: Gonorrhoeae antigens include Por (or porin)protein, such as PorB (see Zhu et al., Vaccine (2004) 22:660-669), atransferring binding protein, such as TbpA and TbpB (See Price et al.,Infection and Immunity (2004) 71(1):277-283), a opacity protein (such asOpa), a reduction-modifiable protein (Rmp), and outer membrane vesicle(OMV) preparations (see Plante et al., J Infectious Disease (2000)182:848-855), also see e.g. WO99/24578, WO99/36544, WO99/57280,WO02/079243).

Chlamydia trachomatis: Chlamydia trachomatis antigens include antigensderived from serotypes A, B, Ba and C (agents of trachoma, a cause ofblindness), serotypes L1, L2 & L3 (associated with Lymphogranulomavenereum), and serotypes, D-K. Chlamydia trachomas antigens may alsoinclude an antigen identified in WO 00/37494, WO 03/049762, WO03/068811, or WO 05/002619, including PepA (CT045), LcrE (CT089), ArtJ(CT381), DnaK (CT396), CT398, OmpH-like (CT242), L7/L12 (CT316), OmcA(CT444), AtosS (CT467), CT547, Eno (CT587), HrtA (CT823), and MurG(CT761).

Treponema pallidum (Syphilis): Syphilis antigens include TmpA antigen.

Haemophilus ducreyi (causing chancroid): Ducreyi antigens include outermembrane protein (DsrA).

Enterococcus faecalis or Enterococcus faecium: Antigens include atrisaccharide repeat or other Enterococcus derived antigens provided inU.S. Pat. No. 6,756,361.

Helicobacter pylori: H. pylori antigens include Cag, Vac, Nap, HopX,HopY and/or urease antigen.

Staphylococcus saprophyticus: Antigens include the 160 kDa hemagglutininof S. saprophyticus antigen.

Yersinia enterocolitica antigens include LPS (Infect Immun. 2002 August;70(8): 4414).

E. coli: E. coli antigens may be derived from enterotoxigenic E. coli(ETEC), enteroaggregative E. coli (EAggEC), diffusely adhering E. coli(DAEC), enteropathogenic E. coli (EPEC), and/or enterohemorrhagic E.coli (EHEC).

Bacillus anthracis (anthrax): B. anthracis antigens are optionallydetoxified and may be selected from A-components (lethal factor (LF) andedema factor (EF)), both of which can share a common B-component knownas protective antigen (PA).

Yersinia pestis (plague): Plague antigens include F1 capsular antigen(Infect Immun. 2003 January; 71(1)): 374-383, LPS (Infect Immun. 1999October; 67(10): 5395), Yersinia pestis V antigen (Infect Immun. 1997November; 65(11): 4476-4482).

Mycobacterium tuberculosis: Tuberculosis antigens include lipoproteins,LPS, BCG antigens, a fusion protein of antigen 85B (Ag85B) and/or ESAT-6optionally formulated in cationic lipid vesicles (Infect Immun. 2004October; 72(10): 6148), Mycobacterium tuberculosis (Mtb) isocitratedehydrogenase associated antigens (Proc Natl Acad Sci USA. 2004 Aug. 24;101(34): 12652), and/or MPT51 antigens (Infect Immun. 2004 July; 72(7):3829).

Rickettsia: Antigens include outer membrane proteins, including theouter membrane protein A and/or B (OmpB) (Biochim Biophys Acta. 2004Nov. 1; 1702(2):145), LPS, and surface protein antigen (SPA) (J.Autoimmun. 1989 June; 2 Suppl:81).

Listeria monocytogenes. Bacterial antigens may be derived from Listeriamonocytogenes.

Chlamydia pneumoniae: Antigens include those identified in WO 02/02606.

Vibrio cholerae: Antigens include proteinase antigens, LPS, particularlylipopolysaccharides of Vibrio cholerae II, O1 Inaba O-specificpolysaccharides, V. cholera O139, antigens of IEM108 vaccine (InfectImmun. 2003 October; 71(10):5498-504), and/or Zonula occludens toxin(Zot).

Salmonella typhi (typhoid fever): Antigens include capsularpolysaccharides preferably conjugates (Vi, i.e. vax-TyVi).

Borrelia burgdorferi (Lyme disease): Antigens include lipoproteins (suchas OspA, OspB, OspC and OspD), other surface proteins such asOspE-related proteins (Erps), decorin-binding proteins (such as DbpA),and antigenically variable VI proteins, such as antigens associated withP39 and P13 (an integral membrane protein, Infect Immun. 2001 May;69(5): 3323-3334), VlsE Antigenic Variation Protein (J Clin Microbiol.1999 December; 37(12): 3997).

Porphyromonas gingivalis: Antigens include P. gingivalis outer membraneprotein (OMP).

Klebsiella: Antigens include an OMP, including OMP A, or apolysaccharide optionally conjugated to tetanus toxoid.

Further bacterial antigens useful in compositions of the invention maybe capsular antigens, polysaccharide antigens or protein antigens of anyof the above. Further bacterial antigens may also include an outermembrane vesicle (OMV) preparation. Additionally, antigens include live,attenuated, and/or purified versions of any of the aforementionedbacteria. The antigens may be derived from gram-negative orgram-positive bacteria. The antigens may be derived from aerobic oranaerobic bacteria.

Additionally, any of the above bacterial-derived saccharides(polysaccharides, LPS, LOS or oligosaccharides) can be conjugated toanother agent or antigen, such as a carrier protein (for exampleCRM197). Such conjugation may be direct conjugation effected byreductive amination of carbonyl moieties on the saccharide to aminogroups on the protein, as provided in U.S. Pat. No. 5,360,897 and Can JBiochem Cell Biol. 1984 May; 62(5):270-5. Alternatively, the saccharidescan be conjugated through a linker, such as, with succinamide or otherlinkages provided in Bioconjugate Techniques, 1996 and CRC, Chemistry ofProtein Conjugation and Cross-Linking, 1993.

B. VIRAL ANTIGENS

Viral antigens suitable for use in the invention include inactivated (orkilled) virus, attenuated virus, split virus formulations, purifiedsubunit formulations, viral proteins which may be isolated, purified orderived from a virus, and Virus Like Particles (VLPs). Viral antigensmay be derived from viruses propagated on cell culture or othersubstrate. Alternatively, viral antigens may be expressed recombinantly.Viral antigens preferably include epitopes which are exposed on thesurface of the virus during at least one stage of its life cycle. Viralantigens are preferably conserved across multiple serotypes or isolates.Viral antigens include antigens derived from one or more of the virusesset forth below as well as the specific antigens examples identifiedbelow.

Orthomyxovirus: Viral antigens may be derived from an Orthomyxovirus,such as Influenza A, B and C. Orthomyxovirus antigens may be selectedfrom one or more of the viral proteins, including hemagglutinin (HA),neuraminidase (NA), nucleoprotein (NP), matrix protein (M1), membraneprotein (M2), one or more of the transcriptase components (PB1, PB2 andPA). Preferred antigens include HA and NA.

Influenza antigens may be derived from interpandemic (annual) flustrains. Alternatively influenza antigens may be derived from strainswith the potential to cause pandemic a pandemic outbreak (i.e.,influenza strains with new haemagglutinin compared to the haemagglutininin currently circulating strains, or influenza strains which arepathogenic in avian subjects and have the potential to be transmittedhorizontally in the human population, or influenza strains which arepathogenic to humans).

Paramyxoviridae viruses: Viral antigens may be derived fromParamyxoviridae viruses, such as Pneumoviruses (RSV), Paramyxoviruses(PIV) and Morbilliviruses (Measles).

Pneumovirus: Viral antigens may be derived from a Pneumovirus, such asRespiratory syncytial virus (RSV), Bovine respiratory syncytial virus,Pneumonia virus of mice, and Turkey rhinotracheitis virus. Preferably,the Pneumovirus is RSV. Pneumovirus antigens may be selected from one ormore of the following proteins, including surface proteins Fusion (F),Glycoprotein (G) and Small Hydrophobic protein (SH), matrix proteins Mand M2, nucleocapsid proteins N, P and L and nonstructural proteins NS 1and NS2. Preferred Pneumovirus antigens include F, G and M. See e.g., JGen Virol. 2004 November; 85(Pt 11):3229). Pneumovirus antigens may alsobe formulated in or derived from chimeric viruses. For example, chimericRSV/PIV viruses may comprise components of both RSV and PIV.

Paramyxovirus: Viral antigens may be derived from a Paramyxovirus, suchas Parainfluenza virus types 1-4 (PIV), Mumps, Sendai viruses, Simianvirus 5, Bovine parainfluenza virus and Newcastle disease virus.Preferably, the Paramyxovirus is PIV or Mumps. Paramyxovirus antigensmay be selected from one or more of the following proteins:Hemagglutinin-Neuraminidase (FIN), Fusion proteins F1 and F2,Nucleoprotein (NP), Phosphoprotein (P), Large protein (L), and Matrixprotein (M). Preferred Paramyxovirus proteins include FIN, F1 and F2.Paramyxovirus antigens may also be formulated in or derived fromchimeric viruses. For example, chimeric RSV/PIV viruses may comprisecomponents of both RSV and PIV. Commercially available mumps vaccinesinclude live attenuated mumps virus, in either a monovalent form or incombination with measles and rubella vaccines (MMR).

Morbillivirus: Viral antigens may be derived from a Morbillivirus, suchas Measles. Morbillivirus antigens may be selected from one or more ofthe following proteins: hemagglutinin (H), Glycoprotein (G), Fusionfactor (F), Large protein (L), Nucleoprotein (NP), Polymerasephosphoprotein (P), and Matrix (M). Commercially available measlesvaccines include live attenuated measles virus, typically in combinationwith mumps and rubella (MMR).

Picornavirus: Viral antigens may be derived from Picornaviruses, such asEnteroviruses, Rhinoviruses, Heparnavirus, Cardioviruses andAphthoviruses. Antigens derived from Enteroviruses, such as Poliovirusare preferred.

Enterovirus: Viral antigens may be derived from an Enterovirus, such asPoliovirus types 1, 2 or 3, Coxsackie A virus types 1 to 22 and 24,Coxsackie B virus types 1 to 6, Echovirus (ECHO) virus) types 1 to 9, 11to 27 and 29 to 34 and Enterovirus 68 to 71. Preferably, the Enterovirusis poliovirus. Enterovirus antigens are preferably selected from one ormore of the following Capsid proteins VP1, VP2, VP3 and VP4.Commercially available polio vaccines include Inactivated Polio Vaccine(IPV) and Oral poliovirus vaccine (OPV).

Heparnavirus: Viral antigens may be derived from an Heparnavirus, suchas Hepatitis A virus (HAV). Commercially available HAV vaccines includeinactivated HAV vaccine.

Togavirus: Viral antigens may be derived from a Togavirus, such as aRubivirus, an Alphavirus, or an Arterivirus. Antigens derived fromRubivirus, such as Rubella virus, are preferred. Togavirus antigens maybe selected from E1, E2, E3, C, NSP-1, NSPO-2, NSP-3 or NSP-4. Togavirusantigens are preferably selected from E1, E2 or E3. Commerciallyavailable Rubella vaccines include a live cold-adapted virus, typicallyin combination with mumps and measles vaccines (MMR).

Flavivirus: Viral antigens may be derived from a Flavivirus, such asTick-borne encephalitis (TBE), Dengue (types 1, 2, 3 or 4), YellowFever, Japanese encephalitis, West Nile encephalitis, St. Louisencephalitis, Russian spring-summer encephalitis, Powassan encephalitis.Flavivirus antigens may be selected from PrM, M, C, E, NS-1, NS-2a,NS2b, NS3, NS4a, NS4b, and NS5. Flavivirus antigens are preferablyselected from PrM, M and E. Commercially available TBE vaccine includeinactivated virus vaccines.

Pestivirus: Viral antigens may be derived from a Pestivirus, such asBovine viral diarrhea (BVDV), Classical swine fever (CSFV) or Borderdisease (BDV).

Hepadnavirus: Viral antigens may be derived from a Hepadnavirus, such asHepatitis B virus. Hepadnavirus antigens may be selected from surfaceantigens (L, M and S), core antigens (HBc, HBe). Commercially availableHBV vaccines include subunit vaccines comprising the surface antigen Sprotein.

Hepatitis C virus: Viral antigens may be derived from a Hepatitis Cvirus (HCV). HCV antigens may be selected from one or more of E1, E2,E1/E2, NS345 polyprotein, NS 345-core polyprotein, core, and/or peptidesfrom the nonstructural regions (Houghton et al., Hepatology (1991)14:381).

Rhabdovirus: Viral antigens may be derived from a Rhabdovirus, such as aLyssavirus (Rabies virus) and Vesiculovirus (VSV). Rhabdovirus antigensmay be selected from glycoprotein (G), nucleoprotein (N), large protein(L), nonstructural proteins (NS). Commercially available Rabies virusvaccine comprise killed virus grown on human diploid cells or fetalrhesus lung cells.

Caliciviridae: Viral antigens may be derived from Calciviridae, such asNorwalk virus, and Norwalk-like Viruses, such as Hawaii Virus and SnowMountain Virus.

Coronavirus: Viral antigens may be derived from a Coronavirus, SARS,Human respiratory coronavirus, Avian infectious bronchitis (IBV), Mousehepatitis virus (MHV), and Porcine transmissible gastroenteritis virus(TGEV). Coronavirus antigens may be selected from spike (S), envelope(E), matrix (M), nucleocapsid (N), and Hemagglutinin-esteraseglycoprotein (HE). Preferably, the Coronavirus antigen is derived from aSARS virus. SARS viral antigens are described in WO 04/92360;

Retrovirus: Viral antigens may be derived from a Retrovirus, such as anOncovirus, a Lentivirus or a Spumavirus. Oncovirus antigens may bederived from HTLV-1, HTLV-2 or HTLV-5. Lentivirus antigens may bederived from HIV-1 or HIV-2. Retrovirus antigens may be selected fromgag, pol, env, tax, tat, rex, rev, nef, vif, vpu, and vpr. HIV antigensmay be selected from gag (p24gag and p55gag), env (gp160 and gp41), pol,tat, nef, rev vpu, miniproteins, (preferably p55 gag and gp140v delete).HIV antigens may be derived from one or more of the following strains:HIVIIIb, HIVSF2, HIVLAV, HIVLAI, HIVMN, HIV-1CM235, HIV-1US4.

Reovirus: Viral antigens may be derived from a Reovirus, such as anOrthoreovirus, a Rotavirus, an Orbivirus, or a Coltivirus. Reovirusantigens may be selected from structural proteins λ1, λ2, λ3, μ1, μ2,σ1, σ2, or σ3, or nonstructural proteins σNS, μNS, or σ1s. PreferredReovirus antigens may be derived from a Rotavirus. Rotavirus antigensmay be selected from VP1, VP2, VP3, VP4 (or the cleaved product VP5 andVP8), NSP 1, VP6, NSP3, NSP2, VP7, NSP4, or NSP5. Preferred Rotavirusantigens include VP4 (or the cleaved product VP5 and VP8), and VP7.

Parvovirus: Viral antigens may be derived from a Parvovirus, such asParvovirus B19. Parvovirus antigens may be selected from VP-1, VP-2,VP-3, NS-1 and NS-2. Preferably, the Parvovirus antigen is capsidprotein VP-2.

Delta hepatitis virus (HDV): Viral antigens may be derived HDV,particularly 6-antigen from HDV (see, e.g., U.S. Pat. No. 5,378,814).

Hepatitis E virus (HEV): Viral antigens may be derived from HEV.

Hepatitis G virus (HGV): Viral antigens may be derived from HGV.

Human Herpesvirus: Viral antigens may be derived from a HumanHerpesvirus, such as Herpes Simplex Viruses (HSV), Varicella-zostervirus (VZV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), HumanHerpesvirus 6 (HHV6), Human Herpesvirus 7 (HHV7), and Human Herpesvirus8 (HHV8). Human Herpesvirus antigens may be selected from immediateearly proteins (α), early proteins (β), and late proteins (γ). HSVantigens may be derived from HSV-1 or HSV-2 strains. HSV antigens may beselected from glycoproteins gB, gC, gD and gH, fusion protein (gB), orimmune escape proteins (gC, gE, or gI). VZV antigens may be selectedfrom core, nucleocapsid, tegument, or envelope proteins. A liveattenuated VZV vaccine is commercially available. EBV antigens may beselected from early antigen (EA) proteins, viral capsid antigen (VCA),and glycoproteins of the membrane antigen (MA). CMV antigens may beselected from capsid proteins, envelope glycoproteins (such as gB andgH), and tegument proteins

Papovaviruses: Antigens may be derived from Papovaviruses, such asPapillomaviruses and Polyomaviruses. Papillomaviruses include HPVserotypes 1, 2, 4, 5, 6, 8, 11, 13, 16, 18, 31, 33, 35, 39, 41, 42, 47,51, 57, 58, 63 and 65. Preferably, HPV antigens are derived fromserotypes 6, 11, 16 or 18. HPV antigens may be selected from capsidproteins (L1) and (L2), or E1-E7, or fusions thereof. HPV antigens arepreferably formulated into virus-like particles (VLPs). Polyomyavirusviruses include BK virus and JK virus. Polyomavirus antigens may beselected from VP1, VP2 or VP3.

Further provided are antigens, compositions, methods, and microbesincluded in Vaccines, 4th Edition (Plotkin and Orenstein ed. 2004);Medical Microbiology 4th Edition (Murray et al. ed. 2002); Virology, 3rdEdition (W. K. Joklik ed. 1988); Fundamental Virology, 2nd Edition (B.N. Fields and D. M. Knipe, eds. 1991), which are contemplated inconjunction with the compositions of the present invention.

C. FUNGAL ANTIGENS

Fungal antigens for use in the invention may be derived from one or moreof the fungi set forth below.

Fungal antigens may be derived from Dermatophytres, including:Epidermophyton floccusum, Microsporum audouini, Microsporum canis,Microsporum distortum, Microsporum equinum, Microsporum gypsum,Microsporum nanum, Trichophyton concentricum, Trichophyton equinum,Trichophyton gallinae, Trichophyton gypseum, Trichophyton megnini,Trichophyton mentagrophytes, Trichophyton quinckeanum, Trichophytonrubrum, Trichophyton schoenleini, Trichophyton tonsurans, Trichophytonverrucosum, T. verrucosum var. album, var. discoides, var. ochraceum,Trichophyton violaceum, and/or Trichophyton faviforme.

Fungal pathogens may be derived from Aspergillus fumigatus, Aspergillusflavus, Aspergillus niger, Aspergillus nidulans, Aspergillus terreus,Aspergillus sydowi, Aspergillus flavatus, Aspergillus glaucus,Blastoschizomyces capitatus, Candida albicans, Candida enolase, Candidatropicalis, Candida glabrata, Candida krusei, Candida parapsilosis,Candida stellatoidea, Candida kusei, Candida parakwsei, Candidalusitaniae, Candida pseudotropicalis, Candida guilliermondi,Cladosporium carrionii, Coccidioides immitis, Blastomyces dermatidis,Cryptococcus neoformans, Geotrichum clavatum, Histoplasma capsulatum,Klebsiella pneumoniae, Paracoccidioides brasiliensis, Pneumocystiscarinii, Pythiumn insidiosum, Pityrosporum ovale, Sacharomycescerevisae, Saccharomyces boulardii, Saccharomyces pombe, Scedosporiumapiosperum, Sporothrix schenckii, Trichosporon beigelii, Toxoplasmagondii, Penicillium marneffei, Malassezia spp., Fonsecaea spp.,Wangiella spp., Sporothrix spp., Basidiobolus spp., Conidiobolus spp.,Rhizopus spp, Mucor spp, Absidia spp, Mortierella spp, Cunninghamellaspp, Saksenaea spp., Alternaria spp, Curvularia spp, Helminthosporiumspp, Fusarium spp, Aspergillus spp, Penicillium spp, Monolinia spp,Rhizoctonia spp, Paecilomyces spp, Pithomyces spp, and Cladosporium spp.

Processes for producing a fungal antigens are well known in the art (seeU.S. Pat. No. 6,333,164). In a preferred method a solubilized fractionextracted and separated from an insoluble fraction obtainable fromfungal cells of which cell wall has been substantially removed or atleast partially removed, characterized in that the process comprises thesteps of: obtaining living fungal cells; obtaining fungal cells of whichcell wall has been substantially removed or at least partially removed;bursting the fungal cells of which cell wall has been substantiallyremoved or at least partially removed; obtaining an insoluble fraction;and extracting and separating a solubilized fraction from the insolublefraction.

D. STD ANTIGENS

The compositions of the invention may include one or more antigensderived from a sexually transmitted disease (STD). Such antigens mayprovide for prophylactic or therapy for STDs such as chlamydia, genitalherpes, hepatits (such as HCV), genital warts, gonorrhoea, syphilisand/or chancroid (See, WO00/15255). Antigens may be derived from one ormore viral or bacterial STDs. Viral STD antigens for use in theinvention may be derived from, for example, HIV, herpes simplex virus(HSV-1 and HSV-2), human papillomavirus (HPV), and hepatitis (HCV).Bacterial STD antigens for use in the invention may be derived from, forexample, Neiserria gonorrhoeae, Chlamydia trachomatis, Treponemapallidum, Haemophilus ducreyi, E. coli, and Streptococcus agalactiae.Examples of specific antigens derived from these pathogens are describedabove.

E. RESPIRATORY ANTIGENS

The compositions of the invention may include one or more antigensderived from a pathogen which causes respiratory disease. For example,respiratory antigens may be derived from a respiratory virus such asOrthomyxoviruses (influenza), Pneumovirus (RSV), Paramyxovirus (PIV),Morbillivirus (measles), Togavirus (Rubella), VZV, and Coronavirus(SARS). Respiratory antigens may be derived from a bacteria which causesrespiratory disease, such as Streptococcus pneumoniae, Pseudomonasaeruginosa, Bordetella pertussis, Mycobacterium tuberculosis, Mycoplasmapneumoniae, Chlamydia pneumoniae, Bacillus anthracis, and Moraxellacatarrhalis. Examples of specific antigens derived from these pathogensare described above.

F. PEDIATRIC VACCINE ANTIGENS

The compositions of the invention may include one or more antigenssuitable for use in pediatric subjects. Pediatric subjects are typicallyless than about 3 years old, or less than about 2 years old, or lessthan about 1 years old. Pediatric antigens may be administered multipletimes over the course of 6 months, 1, 2 or 3 years. Pediatric antigensmay be derived from a virus which may target pediatric populationsand/or a virus from which pediatric populations are susceptible toinfection. Pediatric viral antigens include antigens derived from one ormore of Orthomyxovirus (influenza), Pneumovirus (RSV), Paramyxovirus(PIV and Mumps), Morbillivirus (measles), Togavirus (Rubella),Enterovirus (polio), HBV, Coronavirus (SARS), and Varicella-zoster virus(VZV), Epstein Barr virus (EBV). Pediatric bacterial antigens includeantigens derived from one or more of Streptococcus pneumoniae, Neisseriameningitides, Streptococcus agalactiae (Group A Streptococcus),Moraxella catarrhalis, Bordetella pertussis, Staphylococcus aureus,Clostridium tetani (Tetanus), Cornynebacterium diphtheriae (Diphtheria),Haemophilus influenzae B (Hib), Pseudomonas aeruginosa, Streptococcusagalactiae (Group B Streptococcus), and E. coli. Examples of specificantigens derived from these pathogens are described above.

G. ANTIGENS SUITABLE FOR USE IN ELDERLY OR IMMUNOCOMPROMISED INDIVIDUALS

The compositions of the invention may include one or more antigenssuitable for use in elderly or immunocompromised individuals. Suchindividuals may need to be vaccinated more frequently, with higher dosesor with adjuvanted formulations to improve their immune response to thetargeted antigens. Antigens which may be targeted for use in Elderly orImmunocompromised individuals include antigens derived from one or moreof the following pathogens: Neisseria meningitides, Streptococcuspneumoniae, Streptococcus agalactiae (Group A Streptococcus), Moraxellacatarrhalis, Bordetella pertussis, Staphylococcus aureus, Staphylococcusepidermis, Clostridium tetani (Tetanus), Cornynebacterium diphtheriae(Diphtheria), Haemophilus influenzae B (Hib), Pseudomonas aeruginosa,Legionella pneumophila, Streptococcus agalactiae (Group BStreptococcus), Enterococcus faecalis, Helicobacter pylori, Clamydiapneumoniae, Orthomyxovirus (influenza), Pneumovirus (RSV), Paramyxovirus(PIV and Mumps), Morbillivirus (measles), Togavirus (Rubella),Enterovirus (polio), HBV, Coronavirus (SARS), Varicella-zoster virus(VZV), Epstein Barr virus (EBV), Cytomegalovirus (CMV). Examples ofspecific antigens derived from these pathogens are described above.

H. ANTIGENS SUITABLE FOR USE IN ADOLESCENT VACCINES

The compositions of the invention may include one or more antigenssuitable for use in adolescent subjects. Adolescents may be in need of aboost of a previously administered pediatric antigen. Pediatric antigenswhich may be suitable for use in adolescents are described above. Inaddition, adolescents may be targeted to receive antigens derived froman STD pathogen in order to ensure protective or therapeutic immunitybefore the beginning of sexual activity. STD antigens which may besuitable for use in adolescents are described above.

I. ANTIGEN FORMULATIONS

In other aspects of the invention, methods of producing microparticleshaving adsorbed antigens are provided. The methods comprise: (a)providing an emulsion by dispersing a mixture comprising (i) water, (ii)a detergent, (iii) an organic solvent, and (iv) a biodegradable polymerselected from the group consisting of a poly(α-hydroxy acid), apolyhydroxy butyric acid, a polycaprolactone, a polyorthoester, apolyanhydride, and a polycyanoacrylate. The polymer is typically presentin the mixture at a concentration of about 1% to about 30% relative tothe organic solvent, while the detergent is typically present in themixture at a weight-to-weight detergent-to-polymer ratio of from about0.00001:1 to about 0.1:1 (more typically about 0.0001:1 to about 0.1:1,about 0.001:1 to about 0.1:1, or about 0.005:1 to about 0.1:1); (b)removing the organic solvent from the emulsion; and (c) adsorbing anantigen on the surface of the microparticles. In certain embodiments,the biodegradable polymer is present at a concentration of about 3% toabout 10% relative to the organic solvent.

Microparticles for use herein will be formed from materials that aresterilizable, non-toxic and biodegradable. Such materials include,without limitation, poly(α-hydroxy acid), polyhydroxybutyric acid,polycaprolactone, polyorthoester, polyanhydride, PACA, andpolycyanoacrylate. Preferably, microparticles for use with the presentinvention are derived from a poly(α-hydroxy acid), in particular, from apoly(lactide) (“PLA”) or a copolymer of D,L-lactide and glycolide orglycolic acid, such as a poly(D,L-lactide-co-glycolide) (“PLG” or“PLGA”), or a copolymer of D,L-lactide and caprolactone. Themicroparticles may be derived from any of various polymeric startingmaterials which have a variety of molecular weights and, in the case ofthe copolymers such as PLG, a variety of lactide:glycolide ratios, theselection of which will be largely a matter of choice, depending in parton the coadministered macromolecule. These parameters are discussed morefully below.

Further antigens may also include an outer membrane vesicle (OMV)preparation.

Additional formulation methods and antigens (especially tumor antigens)are provided in U.S. Pat. No. 6,884,435.

J. ANTIGEN REFERENCES

The following references include antigens useful in conjunction with thecompositions of the present invention:

-   1 International patent application WO99/24578-   2 International patent application WO99/36544.-   3 International patent application WO99/57280.-   4 International patent application WO00/22430.-   5 Tettelin et al. (2000) Science 287:1809-1815.-   6 International patent application WO96/29412.-   7 Pizza et al. (2000) Science 287:1816-1820.-   8 PCT WO 01/52885.-   9 Bjune et al. (1991) Lancet 338(8775).-   10 Fuskasawa et al. (1999) Vaccine 17:2951-2958.-   11 Rosenqist et al. (1998) Dev. Biol. Strand 92:323-333.-   12 Constantino et al. (1992) Vaccine 10:691-698.-   13 Constantino et al. (1999) Vaccine 17:1251-1263.-   14 Watson (2000) Pediatr Infect Dis J 19:331-332.-   15 Rubin (20000) Pediatr Clin North Am 47:269-285, v.-   16 Jedrzejas (2001) Microbiol Mol Biol Rev 65:187-207.-   17 International patent application filed on 3 Jul. 2001 claiming    priority from GB-0016363.4; WO 02/02606; PCT IB/01/00166.-   18 Kalman et al. (1999) Nature Genetics 21:385-389.-   19 Read et al. (2000) Nucleic Acids Res 28:1397-406.-   20 Shirai et al. (2000) J. Infect. Dis 181(Suppl 3):S524-S527.-   21 International patent application WO99/27105.-   22 International patent application WO00/27994.-   23 International patent application WO00/37494.-   24 International patent application WO99/28475.-   25 Bell (2000) Pediatr Infect Dis J 19:1187-1188.-   26 Iwarson (1995) APMIS 103:321-326.-   27 Gerlich et al. (1990) Vaccine 8 Suppl:S63-68 & 79-80.-   28 Hsu et al. (1999) Clin Liver Dis 3:901-915.-   29 Gastofsson et al. (1996) N. Engl. J. Med. 334-:349-355.-   30 Rappuoli et al. (1991) TIBTECH 9:232-238.-   31 Vaccines (1988) eds. Plotkin & Mortimer. ISBN 0-7216-1946-0.-   32 Del Guidice et al. (1998) Molecular Aspects of Medicine 19:1-70.-   33 International patent application WO93/018150.-   34 International patent application WO99/53310.-   35 International patent application WO98/04702.-   36 Ross et al. (2001) Vaccine 19:135-142.-   37 Sutter et al. (2000) Pediatr Clin North Am 47:287-308.-   38 Zimmerman & Spann (1999) Am Fan Physician 59:113-118, 125-126.-   39 Dreensen (1997) Vaccine 15 Suppl” S2-6.-   40 MMWR Morb Mortal Wkly rep 1998 Jan. 16:47(1):12, 9.-   41 McMichael (2000) Vaccine 19 Suppl 1:S101-107.-   42 Schuchat (1999) Lancer 353(9146):51-6.-   43 GB patent applications 0026333.5, 0028727.6 & 0105640.7.-   44 Dale (1999) Infect Disclin North Am 13:227-43, viii.-   45 Ferretti et al. (2001) PNAS USA 98: 4658-4663.-   46 Kuroda et al. (2001) Lancet 357(9264):1225-1240; see also pages    1218-1219.-   47 Ramsay et al. (2001) Lancet 357(9251):195-196.-   48 Lindberg (1999) Vaccine 17 Suppl 2:S28-36.-   49 Buttery & Moxon (2000) J R Coil Physicians Long 34:163-168.-   50 Ahmad & Chapnick (1999) Infect Dis Clin North Am 13:113-133, vii.-   51 Goldblatt (1998) J. Med. Microbiol. 47:663-567.-   52 European patent 0 477 508.-   53 U.S. Pat. No. 5,306,492.-   54 International patent application WO98/42721.-   55 Conjugate Vaccines (eds. Cruse et al.) ISBN 3805549326,    particularly vol. 10:48-114.-   56 Hermanson (1996) Bioconjugate Techniques ISBN: 012323368 &    012342335X.-   57 European patent application 0372501.-   58 European patent application 58.-   59 European patent application 0427347.-   60 International patent application WO93/17712.-   61 International patent application WO98/58668.-   62 European patent application 0471177.-   63 International patent application WO00/56360.-   64 International patent application WO00/67161.

The contents of all of the above cited patents, patent applications andjournal articles are incorporated by reference as if set forth fullyherein.

Carrier Proteins

Where a saccharide or carbohydrate antigen is used, it is preferablyconjugated to a carrier protein in order to enhance immunogenicity. SeeRamsay et al. (2001) Lancet 357(9251):195-196; Lindberg (1999) Vaccine17 Suppl 2:S28-36; Buttery & Moxon (2000) J R Coll Physicians Lond34:163-168; Ahmad & Chapnick (1999) Infect Dis Clin North Am 13:113-133,vii; Goldblatt (1998) J. Med. Microbiol. 47:563-567; European patent 0477 508; U.S. Pat. No. 5,306,492; WO98/42721; Conjugate Vaccines (eds.Cruse et al.) ISBN 3805549326, particularly vol. 10:48-114; Hermanson(1996) Bioconjugate Techniques ISBN: 0123423368 or 012342335X. Preferredcarrier proteins are bacterial toxins or toxoids, such as diphtheria ortetanus toxoids. The CRM197 diphtheria toxoid is particularly preferred.

Other carrier polypeptides include the N. meningitidis outer membraneprotein (EP-A-0372501), synthetic peptides (EP-A-0378881 and EP-A0427347), heat shock proteins (WO 93/17712 and WO 94/03208), pertussisproteins (WO 98/58668 and EP A 0471177), protein D from H. influenzae(WO 00/56360), cytokines (WO 91/01146), lymphokines, hormones, growthfactors, toxin A or B from C. difficile (WO 00/61761), iron-uptakeproteins (WO 01/72337), etc. Where a mixture comprises capsularsaccharide from both serigraphs A and C, it may be preferred that theratio (w/w) of MenA saccharide:MenC saccharide is greater than 1 (e.g.,2:1, 3:1, 4:1, 5:1, 10:1 or higher). Different saccharides can beconjugated to the same or different type of carrier protein. Anysuitable conjugation reaction can be used, with any suitable linkerwhere necessary.

Toxic protein antigens may be detoxified where necessary e.g.,detoxification of pertussis toxin by chemical and/or genetic means.

Pharmaceutically Acceptable Carriers

Compositions of the invention will typically, in addition to thecomponents mentioned above, comprise one or more pharmaceuticallyacceptable carriers. These include any carrier which does not itselfinduce the production of antibodies harmful to the individual receivingthe composition. Suitable carriers typically are large, slowlymetabolized macromolecules such as proteins, polysaccharides, polylacticacids, polyglycolic acids, polymeric amino acids, amino acid copolymers,and lipid aggregates (such as oil droplets or liposomes). Such carriersare well known to those of ordinary skill in the art. A composition mayalso contain a diluent, such as water, saline, glycerol, etc.Additionally, an auxiliary substance, such as a wetting or emulsifyingagent, pH buffering substance, and the like, may be present. A thoroughdiscussion of pharmaceutically acceptable components is available inGennaro (2000) Remington: The Science and Practice of Pharmacy. 20thed., ISBN: 0683306472.

Immunoregulatory Agents

Adjuvants

Vaccines of the invention may be administered in conjunction with otherimmunoregulatory agents. In particular, compositions will usuallyinclude an adjuvant. Adjuvants for use with the invention include, butare not limited to, one or more of the following set forth below:

A. Mineral Containing Compositions

Mineral containing compositions suitable for use as adjuvants in theinvention include mineral salts, such as aluminum salts and calciumsalts. The invention includes mineral salts such as hydroxides (e.g.oxyhydroxides), phosphates (e.g. hydroxyphosphates, orthophosphates),sulfates, etc. (e.g. see chapters 8 & 9 of Vaccine Design . . . (1995)eds. Powell & Newman. ISBN: 030644867X. Plenum.), or mixtures ofdifferent mineral compounds (e.g. a mixture of a phosphate and ahydroxide adjuvant, optionally with an excess of the phosphate), withthe compounds taking any suitable form (e.g. gel, crystalline,amorphous, etc.), and with adsorption to the salt(s) being preferred.The mineral containing compositions may also be formulated as a particleof metal salt (WO00/23105).

Aluminum salts may be included in vaccines of the invention such thatthe dose of Al³⁺ is between 0.2 and 1.0 mg per dose.

In one embodiment the aluminum based adjuvant for use in the presentinvention is alum (aluminum potassium sulfate (AlK(SO₄)₂)), or an alumderivative, such as that formed in-situ by mixing an antigen inphosphate buffer with alum, followed by titration and precipitation witha base such as ammonium hydroxide or sodium hydroxide.

Another aluminum-based adjuvant for use in vaccine formulations of thepresent invention is aluminum hydroxide adjuvant (Al(OH)₃) orcrystalline aluminum oxyhydroxide (AlOOH), which is an excellentadsorbant, having a surface area of approximately 500 m²/g.Alternatively, aluminum phosphate adjuvant (AlPO₄) or aluminumhydroxyphosphate, which contains phosphate groups in place of some orall of the hydroxyl groups of aluminum hydroxide adjuvant is provided.Preferred aluminum phosphate adjuvants provided herein are amorphous andsoluble in acidic, basic and neutral media.

In another embodiment the adjuvant of the invention comprises bothaluminum phosphate and aluminum hydroxide. In a more particularembodiment thereof, the adjuvant has a greater amount of aluminumphosphate than aluminum hydroxide, such as a ratio of 2:1, 3:1, 4:1,5:1, 6:1, 7:1, 8:1, 9:1 or greater than 9:1, by weight aluminumphosphate to aluminum hydroxide. More particular still, aluminum saltsin the vaccine are present at 0.4 to 1.0 mg per vaccine dose, or 0.4 to0.8 mg per vaccine dose, or 0.5 to 0.7 mg per vaccine dose, or about 0.6mg per vaccine dose.

Generally, the preferred aluminum-based adjuvant(s), or ratio ofmultiple aluminum-based adjuvants, such as aluminum phosphate toaluminum hydroxide is selected by optimization of electrostaticattraction between molecules such that the antigen carries an oppositecharge as the adjuvant at the desired pH. For example, aluminumphosphate adjuvant (isoelectric point=4) adsorbs lysozyme, but notalbumin at pH 7.4. Should albumin be the target, aluminum hydroxideadjuvant would be selected (iep 11.4). Alternatively, pretreatment ofaluminum hydroxide with phosphate lowers its isoelectric point, makingit a preferred adjuvant for more basic antigens.

B. Oil-Emulsions

Oil-emulsion compositions suitable for use as adjuvants in the inventioninclude squalene-water emulsions, such as 5% squalene, 0.5%polyoxyethylene (20) sorbitan monooleate (polysorbate 80, e.g., TWEEN®80), and 0.5% sorbitan trioleate (e.g., SPAN® 85), such as MF59®,formulated into submicron particles using a microfluidizer). SeeWO90/14837. See also, Podda, Vaccine (2001) 19: 2673-2680; Frey et al.,Vaccine (2003) 21:4234-4237. MF59® is used as the adjuvant in the FLUAD™influenza virus trivalent subunit vaccine.

Particularly preferred adjuvants for use in the compositions aresubmicron oil-in-water emulsions. Preferred submicron oil-in-wateremulsions for use herein are squalene/water emulsions optionallycontaining varying amounts of MTP-PE, such as a submicron oil-in-wateremulsion containing 4-5% w/v squalene, 0.25-1.0% w/v TWEEN™ 80(polyoxyelthylenesorbitan monooleate), and/or 0.25-1.0% SPAN 85™(sorbitan trioleate), and, optionally,N-acetylmuramyl-L-alanyl-D-isogluatminyl-L-alanine-2-(1′-2′-dipalmitoyl-sn-glycero-3-huydroxyphosphosphoryloxy)ethylamine (MTP-PE), for example, the submicron oil-in-water emulsionknown as “MF59” (International Publication No. WO90/14837; U.S. Pat.Nos. 6,299,884 and 6,451,325, and Ott et al., in Vaccine Design: TheSubunit and Adjuvant Approach (Powell, M. F. and Newman, M. J. eds.)Plenum Press, New York, 1995, pp. 277-296). MF59 contains 4-5% w/vSqualene (e.g. 4.3%), 0.25-0.5% w/v TWEEN™ 80, and 0.5% w/v SPAN 85™ andoptionally contains various amounts of MTP-PE, formulated into submicronparticles using a microfluidizer such as Model 110Y microfluidizer(Microfluidics, Newton, Mass.). For example, MTP-PE may be present in anamount of about 0-500 μg/dose, more preferably O-250 μg/dose and mostpreferably, 0-100 μg/dose. As used herein, the term “MF59-0” refers tothe above submicron oil-in-water emulsion lacking MTP-PE, while the termMF59-MTP denotes a formulation that contains MTP-PE. For instance,“MF59-100” contains 100 μg MTP-PE per dose, and so on. MF69, anothersubmicron oil-in-water emulsion for use herein, contains 4.3% w/vsqualene, 0.25% w/v polyoxyethylene (20) sorbitan monooleate(polysorbate 80, e.g., TWEEN® 80), and 0.75% w/v sorbitan trioleate(e.g., SPAN® 85) and optionally MTP-PE. Yet another submicronoil-in-water emulsion is MF75, also known as SAF, containing 10%squalene, 0.4% polyoxyethylene (20) sorbitan monooleate (polysorbate 80,e.g., TWEEN® 80), 5% pluronic-blocked polymer L121, and thr-MDP, alsomicrofluidized into a submicron emulsion. MF75-MTP denotes an MF75formulation that includes MTP, such as from 100-400 μg MTP-PE per dose.

Submicron oil-in-water emulsions, methods of making the same andimmunostimulating agents, such as muramyl peptides, for use in thecompositions, are described in detail in WO90/14837 and U.S. Pat. Nos.6,299,884 and 6,451,325.

Complete Freund's adjuvant (CFA) and incomplete Freund's adjuvant (IFA)may also be used as adjuvants in the invention.

C. Saponin Formulations

Saponin formulations, may also be used as adjuvants in the invention.Saponins are a heterologous group of sterol glycosides and triterpenoidglycosides that are found in the bark, leaves, stems, roots and evenflowers of a wide range of plant species. Saponins isolated from thebark of the Quillaia saponaria Molina tree have been widely studied asadjuvants. Saponins can also be commercially obtained from Smilax ornata(sarsaprilla), Gypsophilla paniculata (brides veil), and Saponariaofficianalis (soap root). Saponin adjuvant formulations include purifiedformulations, such as QS21, as well as lipid formulations, such asISCOMs.

Saponin compositions have been purified using High Performance ThinLayer Chromatography (HP-TLC) and Reversed Phase High Performance LiquidChromatography (RP-HPLC). Specific purified fractions using thesetechniques have been identified, including QS7, QS17, QS18, QS21, QH-A,QH-B and QH-C. Preferably, the saponin is QS21. A method of productionof QS21 is disclosed in U.S. Pat. No. 5,057,540. Saponin formulationsmay also comprise a sterol, such as cholesterol (see WO96/33739).

Combinations of saponins and cholesterols can be used to form uniqueparticles called Immunostimulating Complexes (ISCOMs). ISCOMs typicallyalso include a phospholipid such as phosphatidylethanolamine orphosphatidylcholine. Any known saponin can be used in ISCOMs.Preferably, the ISCOM includes one or more of Quil A, QHA and QHC.ISCOMs are further described in EP0109942, WO96/11711 and WO96/33739.Optionally, the ISCOMS may be devoid of (an) additional detergent(s).See WO00/07621.

A review of the development of saponin based adjuvants can be found inBarr, et al., Advanced Drug Delivery Reviews (1998) 32:247-271. See alsoSjolander, et al., Advanced Drug Delivery Reviews (1998) 32:321-338.

D. Virosomes and Virus Like Particles (VLPs)

Virosomes and Virus Like Particles (VLPs) can also be used as adjuvantsin the invention. These structures generally contain one or moreproteins from a virus optionally combined or formulated with aphospholipid. They are generally non-pathogenic, non-replicating andgenerally do not contain any of the native viral genome. The viralproteins may be recombinantly produced or isolated from whole viruses.These viral proteins suitable for use in virosomes or VLPs includeproteins derived from influenza virus (such as HA or NA), Hepatitis Bvirus (such as core or capsid proteins), Hepatitis E virus, measlesvirus, Sindbis virus, Rotavirus, Foot-and-Mouth Disease virus,Retrovirus, Norwalk virus, human Papilloma virus, HIV, RNA-phages,Q13-phage (such as coat proteins), GA-phage, fr-phage, AP205 phage, andTy (such as retrotransposon Ty protein p1). VLPs are discussed furtherin WO03/024480, WO03/024481, and Niikura et al., Virology (2002)293:273-280; Lenz et al., Journal of Immunology (2001) 5246-5355; Pinto,et al., Journal of Infectious Diseases (2003) 188:327-338; and Gerber etal., Journal of Virology (2001) 75(10):4752-4760. Virosomes arediscussed further in, for example, Gluck et al., Vaccine (2002)20:B10-B16. Immunopotentiating reconstituted influenza virosomes (IRIV)are used as the subunit antigen delivery system in the intranasaltrivalent INFLEXAL™ product {Mischler & Metcalfe (2002) Vaccine 20 Suppl5:B17-23} and the INFLUVAC PLUS™ product.

E. Bacterial or Microbial Derivatives

Adjuvants suitable for use in the invention include bacterial ormicrobial derivatives such as:

(1) Non-Toxic Derivatives of Enterobacterial Lipopolysaccharide (LPS)

Such derivatives include Monophosphoryl lipid A (MPL) and 3-O-deacylatedMPL (3dMPL). 3dMPL is a mixture of 3 De-O-acylated monophosphoryl lipidA with 4, 5 or 6 acylated chains. A preferred “small particle” form of 3De-O-acylated monophosphoryl lipid A is disclosed in EP 0 689 454. Such“small particles” of 3dMPL are small enough to be sterile filteredthrough a 0.22 micron membrane (see EP 0 689 454). Other non-toxic LPSderivatives include monophosphoryl lipid A mimics, such as aminoalkylglucosaminide phosphate derivatives e.g. RC 529. See Johnson et al.(1999) Bioorg Med Chem Lett 9:2273-2278.

(2) Lipid A Derivatives

Lipid A derivatives include derivatives of lipid A from Escherichia colisuch as OM-174. OM-174 is described for example in Meraldi et al.,Vaccine (2003) 21:2485-2491; and Pajak, et al., Vaccine (2003)21:836-842.

(3) Immunostimulatory Oligonucleotides

Immunostimulatory oligonucleotides suitable for use as adjuvants in theinvention include nucleotide sequences containing a CpG motif (asequence containing an unmethylated cytosine followed by guanosine andlinked by a phosphate bond). Bacterial double stranded RNA oroligonucleotides containing palindromic or poly(dG) sequences have alsobeen shown to be immunostimulatory.

The CpGs can include nucleotide modifications/analogs such asphosphorothioate modifications and can be double-stranded orsingle-stranded. Optionally, the guanosine may be replaced with ananalog such as 2′-deoxy-7-deazaguanosine. See Kandimalla, et al.,Nucleic Acids Research (2003) 31(9): 2393-2400; WO02/26757 andWO99/62923 for examples of possible analog substitutions. The adjuvanteffect of CpG oligonucleotides is further discussed in Krieg, NatureMedicine (2003) 9(7): 831-835; McCluskie, et al., FEMS Immunology andMedical Microbiology (2002) 32:179-185; WO98/40100; U.S. Pat. No.6,207,646; U.S. Pat. No. 6,239,116 and U.S. Pat. No. 6,429,199.

The CpG sequence may be directed to TLR9, such as the motif GTCGTT orTTCGTT. See Kandimalla, et al., Biochemical Society Transactions (2003)31 (part 3): 654-658. The CpG sequence may be specific for inducing aTh1 immune response, such as a CpG-A ODN, or it may be more specific forinducing a B cell response, such a CpG-B ODN. CpG-A and CpG-B ODNs arediscussed in Blackwell, et al., J. Immunol. (2003) 170(8):4061-4068;Krieg, TRENDS in Immunology (2002) 23(2): 64-65 and WO01/95935.Preferably, the CpG is a CpG-A ODN.

Preferably, the CpG oligonucleotide is constructed so that the 5′ end isaccessible for receptor recognition. Optionally, two CpG oligonucleotidesequences may be attached at their 3′ ends to form immunomers. See, forexample, Kandimalla, et al., BBRC (2003) 306:948-953; Kandimalla, etal., Biochemical Society Transactions (2003) 31(part 3):664-658; Bhagatet al., BBRC (2003) 300:853-861 and WO03/035836.

(4) ADP-Ribosylating Toxins and Detoxified Derivatives Thereof.

Bacterial ADP-ribosylating toxins and detoxified derivatives thereof maybe used as adjuvants in the invention. Preferably, the protein isderived from E. coli (i.e., E. coli heat labile enterotoxin “LT),cholera (“CT”), or pertussis (“PT”). The use of detoxifiedADP-ribosylating toxins as mucosal adjuvants is described in WO95/17211and as parenteral adjuvants in WO98/42375. Preferably, the adjuvant is adetoxified LT mutant such as LT-K63, LT-R72, and LTR192G. The use ofADP-ribosylating toxins and detoxified derivatives thereof, particularlyLT-K63 and LT-R72, as adjuvants can be found in the followingreferences: Beignon et al., Infection and Immunity (2002)70(6):3012-3019; Pizza, et al., Vaccine (2001) 19:2534-2541; Pizza, etal., Int. J. Med. Microbiol. (2000) 290(4-5):455-461; Scharton-Kerstenet al., Infection and Immunity (2000) 68(9):5306-5313; Ryan et al.,Infection and Immunity (1999) 67(12):6270-6280; Partidos et al.,Immunol. Lett. (1999) 67(3):209-216; Peppoloni et al., Vaccines (2003)2(2):285-293; and Pine et al., (2002) J. Control Release (2002)85(1-3):263-270. Numerical reference for amino acid substitutions ispreferably based on the alignments of the A and B subunits ofADP-ribosylating toxins set forth in Domenighini et al., Mol. Microbiol.(1995) 15(6):1165-1167.

F. Bioadhesives and Mucoadhesives

Bioadhesives and mucoadhesives may also be used as adjuvants in theinvention. Suitable bioadhesives include esterified hyaluronic acidmicrospheres (Singh et al. (2001) J. Cont. Rele. 70:267-276) ormucoadhesives such as cross-linked derivatives of polyacrylic acid,polyvinyl alcohol, polyvinyl pyrollidone, polysaccharides andcarboxymethylcellulose. Chitosan and derivatives thereof may also beused as adjuvants in the invention. See WO99/27960.

G. Microparticles

Microparticles may also be used as adjuvants in the invention.Microparticles (i.e. a particle of ˜100 nm to ˜150 μm in diameter, morepreferably ˜200 nm to ˜30 μm in diameter, and most preferably ˜500 nm to˜10 μm in diameter) formed from materials that are biodegradable and nontoxic (e.g. a poly(α-hydroxy acid), a polyhydroxybutyric acid, apolyorthoester, a polyanhydride, a polycaprolactone, etc.), withpoly(lactide co glycolide) are preferred, optionally treated to have anegatively-charged surface (e.g. with SDS) or a positively-chargedsurface (e.g. with a cationic detergent, such as CTAB).

H. Liposomes

Examples of liposome formulations suitable for use as adjuvants aredescribed in U.S. Pat. No. 6,090,406, U.S. Pat. No. 5,916,588, and EP 0626 169.

I. Polyoxyethylene Ether and Polyoxyethylene Ester Formulations

Adjuvants suitable for use in the invention include polyoxyethyleneethers and polyoxyethylene esters. WO99/52549. Such formulations furtherinclude polyoxyethylene sorbitan ester surfactants in combination withan octoxynol (WO01/21207) as well as polyoxyethylene alkyl ethers orester surfactants in combination with at least one additional non-ionicsurfactant such as an octoxynol (WO01/21152).

Preferred polyoxyethylene ethers are selected from the following group:polyoxyethylene-9-lauryl ether (laureth 9), polyoxyethylene-9-steorylether, polyoxytheylene-8-steoryl ether, polyoxyethylene-4-lauryl ether,polyoxyethylene-35-lauryl ether, and polyoxyethylene-23-lauryl ether.

J. Polyphosphazene (PCPP)

PCPP formulations are described, for example, in Andrianov et al.,“Preparation of hydrogel microspheres by coacervation of aqueouspolyphophazene solutions”, Biomaterials (1998) 19(1-3):109-115 and Payneet al., “Protein Release from Polyphosphazene Matrices”, Adv. Drug.Delivery Review (1998) 31(3):185-196.

K. Muramyl Peptides

Examples of muramyl peptides suitable for use as adjuvants in theinvention include N-acetyl-muramyl-L-threonyl-D-isoglutamine (thr-MDP),N-acetyl-normuramyl-1-alanyl-d-isoglutamine (nor-MDP), and Nacetylmuramyl-1-alanyl-d-isoglutaminyl-1-alanine-2-(1′-2′-dipalmitoyl-snglycero-3-hydroxyphosphoryloxy) ethylamine MTP-PE).

L. Imidazoquinoline Compounds

Examples of imidazoquinoline compounds suitable for use adjuvants in theinvention include Imiquimod and its analogues, described further inStanley, Clin Exp Dermatol (2002) 27(7):571-577; Jones, Curr OpinInvestig Drugs (2003) 4(2):214-218; and U.S. Pat. Nos. 4,689,338,5,389,640, 5,268,376, 4,929,624, 5,266,575, 5,352,784, 5,494,916,5,482,936, 5,346,905, 5,395,937, 5,238,944, and 5,525,612.

M. Thiosemicarbazone Compounds

Examples of thiosemicarbazone compounds, as well as methods offormulating, manufacturing, and screening for compounds all suitable foruse as adjuvants in the invention include those described in WO04/60308.The thiosemicarbazones are particularly effective in the stimulation ofhuman peripheral blood mononuclear cells for the production ofcytokines, such as TNF-α.

N. Tryptanthrin Compounds

Examples of tryptanthrin compounds, as well as methods of formulating,manufacturing, and screening for compounds all suitable for use asadjuvants in the invention include those described in WO04/64759. Thetryptanthrin compounds are particularly effective in the stimulation ofhuman peripheral blood mononuclear cells for the production ofcytokines, such as TNF-α.

The invention may also comprise combinations of aspects of one or moreof the adjuvants identified above. For example, the following adjuvantcompositions may be used in the invention:

-   -   (1) a saponin and an oil-in-water emulsion (WO99/11241);    -   (2) a saponin (e.g., QS21)+a non-toxic LPS derivative (e.g.        3dMPL) (see WO94/00153);    -   (3) a saponin (e.g., QS21)+a non-toxic LPS derivative (e.g.        3dMPL)+a cholesterol;    -   (4) a saponin (e.g., QS21)+3dMPL+IL 12 (optionally+a sterol)        (WO98/57659);    -   (5) combinations of 3dMPL with, for example, QS21 and/or        oil-in-water emulsions (See European patent applications        0835318, 0735898 and 0761231);    -   (6) SAF, containing 10% Squalane, 0.4% Tween 80, 5%        pluronic-block polymer L121, and thr-MDP, either microfluidized        into a submicron emulsion or vortexed to generate a larger        particle size emulsion.    -   (7) RIBI™ adjuvant system (RAS), (Ribi Immunochem) containing 2%        Squalene, 0.2% Tween 80, and one or more bacterial cell wall        components from the group consisting of monophosphorylipid A        (MPL), trehalose dimycolate (TDM), and cell wall skeleton (CWS),        preferably MPL+CWS (DETOX™); and    -   (8) one or more mineral salts (such as an aluminum salt)+a        non-toxic derivative of LPS (such as 3dPML).    -   (9) one or more mineral salts (such as an aluminum salt)+an        immunostimulatory oligonucleotide (such as a nucleotide sequence        including a CpG motif).

O. Human Immunomodulators

Human immunomodulators suitable for use as adjuvants in the inventioninclude cytokines, such as interleukins (e.g. IL-1, IL-2, IL-4, IL-5,IL-6, IL-7, IL-12, etc.), interferons (e.g. interferon-γ), macrophagecolony stimulating factor, and tumor necrosis factor.

Aluminum salts and MF59 are preferred adjuvants for use with injectableinfluenza vaccines. Bacterial toxins and bioadhesives are preferredadjuvants for use with mucosally-delivered vaccines, such as nasalvaccines.

The contents of all of the above cited patents, patent applications andjournal articles are incorporated by reference as if set forth fullyherein.

Therapeutic Methods

The invention provides methods for inducing or increasing an immuneresponse to one or more gram positive (e.g., streptococcal and/orstaphylococcal) bacteria (e.g., S. agalactiae, S. pyogenes, S.pneumoniae, and/or S. aureus) using the compositions described above.The immune response is preferably protective and can include antibodiesand/or cell-mediated immunity (including systemic and mucosal immunity).Immune responses include booster responses.

Teenagers and children, including toddles and infants, can receive avaccine for prophylactic use; therapeutic vaccines typically areadministered to teenagers or adults. A vaccine intended for children mayalso be administered to adults e.g., to assess safety, dosage,immunogenicity, etc.

Diseases caused by S. agalactiae which can be prevented or treatedaccording to the invention include, but are not limited to, newbornsepsis, meningitis and pneumonia and pregnant women infection such as inthe womb, in the amniotic fluid, following cesarean sections, and in theurinary tract.

Diseases caused by S. pneumoniae which can be prevented or treatedaccording to the invention include, but are not limited to, Pneumonia,bacteremia, otitis media, meningitis, sinusitis, peritonitis, andarthritis.

Diseases caused by S. pyogenes which can be prevented or treatedaccording to the invention include, but are not limited to, erysipelaspharyngitis (such as streptococcal sore throat), scarlet fever,impetigo, cellulitis, septicemia, necrotizing fasciitis, myositis, toxicshock syndrome, and sequelae such as rheumatic fever and acuteglomerulonephritis.

Diseases caused by S. aureus which can be prevented or treated accordingto the invention include, but are not limited to, minor skin infections,impetigo, boils, cellulitis folliculitis, furuncles, carbuncles, scaldedskin syndrome, abscesses, pneumonia, meningitis, osteomyelitis,endocarditis, Toxic shock syndrome, and septicemia.

Diseases caused by S. suis which can be prevented or treated accordingto the invention include, but are not limited to, S. suis infections inswine and meningitis, septicemia, pneumonia, endocarditis, arthritis,and septic shock in humans exposed to swine or swine products.

Diseases caused by S. equi which can be prevented or treated accordingto the invention include, but are not limited to, “strangles” in equine,canine and Camelid patients (e.g., horses, donkeys, mules, dogs, camelsand dromedaries) and metastatic strangles.

Diseases caused by S. uberis which can be prevented or treated accordingto the invention include, but are not limited to, mastitis in cattle.

Diseases caused by S. dysgalactiae which can be prevented or treatedaccording to the invention include, but are not limited to, mastitis in,e.g., horses, cattle, and swine.

Diseases caused by S. iniae which can be prevented or treated accordingto the invention include, but are not limited to, S. iniae infection offish and invasive infection in humans after skin injuries during thehandling of infected fish.

Tests to Determine the Efficacy of the Immune Response

One way of assessing efficacy of therapeutic treatment involvesmonitoring bacterial infection after administration of the compositionof the invention. One way of assessing efficacy of prophylactictreatment involves monitoring immune responses against the Cna_B domainsin the compositions of the invention after administration of thecomposition.

Another way of assessing the immunogenicity of the component proteins ofthe immunogenic compositions of the present invention is to produceCna_B domains recombinantly and to screen patient sera or mucosalsecretions by immunoblot. A positive reaction between the protein andthe patient serum indicates that the patient has previously mounted animmune response to the protein in question; i.e., the protein is animmunogen. This method may also be used to identify immunodominantproteins and/or epitopes.

Another way of checking efficacy of therapeutic treatment involvesmonitoring infection after administration of the compositions of theinvention. One way of checking efficacy of prophylactic treatmentinvolves monitoring immune responses both systemically (such asmonitoring the level of IgG1 and IgG2a production) and mucosally (suchas monitoring the level of IgA production) against a Cna_B domain afteradministration of the composition. Typically, serum specific antibodyresponses are determined post-immunization but pre-challenge whereasmucosal specific antibody body responses are determinedpost-immunization and post-challenge.

The vaccine compositions of the present invention can be evaluated in invitro and in vivo animal models prior to host, e.g., human,administration. Particularly useful mouse models include those in whichintraperitoneal immunization is followed by either intraperitonealchallenge or intranasal challenge.

The efficacy of immunogenic compositions of the invention can also bedetermined in vivo by challenging animal models with gram positive(e.g., staphylococal or streptococcal) bacteria, e.g., guinea pigs ormice, with the immunogenic compositions. The immunogenic compositionsmay or may not be derived from the same serotypes as the challengeserotypes.

In vivo efficacy models include but are not limited to: (i) a murineinfection model using human gram positive (e.g., streptococcal and/orstaphylococcal) bacteria serotypes; (ii) a murine disease model which isa murine model using a mouse-adapted streptococcal strain, such as theM23 strain of S. pyogenes which is particularly virulent in mice, and(iii) a primate model using human streptococcal isolates. Other in vivomodels are disclosed in the Examples below.

The immune response may be one or both of a Th1 immune response and aTh2 response. The immune response may be an improved or an enhanced oran altered immune response. The immune response may be one or both of asystemic and a mucosal immune response. Preferably the immune responseis an enhanced system and/or mucosal response.

An enhanced systemic and/or mucosal immunity is reflected in an enhancedTh1 and/or Th2 immune response. Preferably, the enhanced immune responseincludes an increase in the production of IgG1 and/or IgG2a and/or IgA.

Preferably the mucosal immune response is a Th2 immune response.Preferably, the mucosal immune response includes an increase in theproduction of IgA.

Activated Th2 cells enhance antibody production and are therefore ofvalue in responding to extracellular infections. Activated Th2 cells maysecrete one or more of IL-4, IL-5, IL-6, and IL-10. A Th2 immuneresponse may result in the production of IgG1, IgE, IgA and memory Bcells for future protection.

A Th2 immune response may include one or more of an increase in one ormore of the cytokines associated with a Th2 immune response (such asIL-4, IL-5, IL-6 and IL-10), or an increase in the production of IgG1,IgE, IgA and memory B cells. Preferably, the enhanced Th2 immuneresponse will include an increase in IgG1 production.

A Th1 immune response may include one or more of an increase in CTLs, anincrease in one or more of the cytokines associated with a Th1 immuneresponse (such as IL-2, IFNγ, and TNFβ), an increase in activatedmacrophages, an increase in NK activity, or an increase in theproduction of IgG2a. Preferably, the enhanced Th1 immune response willinclude an increase in IgG2a production.

Immunogenic compositions of the invention, in particular, immunogeniccomposition comprising one or more Cna_B domains of the presentinvention may be used either alone or in combination with other grampositive bacterial antigens (e.g., streptococcal or staphylococcalantigens), optionally with an immunoregulatory agent capable ofeliciting a Th1 and/or Th2 response.

The invention also comprises an immunogenic composition comprising oneor more immunoregulatory agent, such as a mineral salt, such as analuminium salt and an oligonucleotide containing a CpG motif. Mostpreferably, the immunogenic composition includes both an aluminium saltand an oligonucleotide containing a CpG motif. Alternatively, theimmunogenic composition includes an ADP ribosylating toxin, such as adetoxified ADP ribosylating toxin and an oligonucleotide containing aCpG motif. Preferably, one or more of the immunoregulatory agentsinclude an adjuvant. The adjuvant may be selected from one or more ofthe group consisting of a Th1 adjuvant and Th2 adjuvant.

The compositions of the invention will preferably elicit both a cellmediated immune response as well as a humoral immune response in orderto effectively address a gram positive bacterial (e.g., streptococcaland/or staphylococcal) infection. This immune response will preferablyinduce long lasting (e.g., neutralizing) antibodies and a cell mediatedimmunity that can quickly respond upon exposure to one or more grampositive bacterial (e.g., streptococcal and/or staphylococcal) antigens.

In one particularly preferred embodiment, the immunogenic compositioncomprises one or more Cna_B domain antigen(s) which elicit(s) aneutralizing antibody response and one or more Cna_B domain antigen (s)which elicit(s) a cell mediated immune response. In this way, theneutralizing antibody response prevents or inhibits an initial grampositive bacterial (e.g., streptococcal and/or staphylococcal) infectionwhile the cell-mediated immune response capable of eliciting an enhancedTh1 cellular response prevents further spreading of the gram positivebacterial (e.g., streptococcal and/or staphylococcal) infection.

Compositions of the invention will generally be administered directly toa patient. The compositions of the present invention may beadministered, either alone or as part of a composition, via a variety ofdifferent routes. Certain routes may be favored for certaincompositions, as resulting in the generation of a more effective immuneresponse, preferably a CMI response, or as being less likely to induceside effects, or as being easier for administration.

Delivery methods include parenteral injection (e.g., subcutaneous,intraperitoneal, intravenous, intramuscular, or interstitial injection)and rectal, oral (e.g., tablet, spray), vaginal, topical, transdermal(e.g., see WO 99/27961), transcutaneous (e.g., see WO02/074244 andWO02/064162), intranasal (e.g., see WO03/028760), ocular, aural, andpulmonary or other mucosal administration.

By way of example, the compositions of the present invention may beadministered via a systemic route or a mucosal route or a transdermalroute or it may be administered directly into a specific tissue. As usedherein, the term “systemic administration” includes but is not limitedto any parenteral routes of administration. In particular, parenteraladministration includes but is not limited to subcutaneous,intraperitoneal, intravenous, intraarterial, intramuscular, orintrasternal injection, intravenous, intraarterial, or kidney dialyticinfusion techniques. Preferably, the systemic, parenteral administrationis intramuscular injection. As used herein, the term “mucosaladministration” includes but is not limited to oral, intranasal,intravaginal, intrarectal, intratracheal, intestinal and ophthalmicadministration.

Dosage treatment can be a single dose schedule or a multiple doseschedule. Multiple doses may be used in a primary immunization scheduleand/or in a booster immunization schedule. In a multiple dose schedulethe various doses may be given by the same or different routes e.g., aparenteral prime and mucosal boost, a mucosal prime and parenteralboost, etc.

The compositions of the invention may be prepared in various forms. Forexample, a composition can be prepared as an injectable, either as aliquid solution or a suspension. Solid forms suitable for solution in,or suspension in, liquid vehicles prior to injection can also beprepared (e.g., a lyophilized composition). A composition can beprepared for oral administration, such as a tablet or capsule, as aspray, or as a syrup (optionally flavored). A composition can beprepared for pulmonary administration, e.g., as an inhaler, using a finepowder or a spray. A composition can be prepared as a suppository orpessary. A composition can be prepared for nasal, aural or ocularadministration e.g., as drops. A composition can be in kit form,designed such that a combined composition is reconstituted just prior toadministration to a patient. Such kits may comprise one or more Cna_Bdomain antigens or other antigens in liquid form and one or morelyophilized antigens.

Immunogenic compositions used as vaccines comprise an immunologicallyeffective amount of one or more Cna_B domain antigens (or nucleic acidmolecules encoding the antigens), as well as any other components, asneeded, such as antibiotics. An “immunologically effective amount” is anamount which, when administered to an individual, either in a singledose or as part of a series, increases a measurable immune response orprevents or reduces a clinical symptom.

The immunogenic compositions of the present invention may beadministered in combination with an antibiotic treatment regime. In oneembodiment, the antibiotic is administered prior to administration ofthe one or more Cna_B domain antigens (or nucleic acid moleculesencoding the antigens) of the invention.

In another embodiment, the antibiotic is administered subsequent to theadministration of a Cna_B domain antigen of the invention. Examples ofantibiotics suitable for use in the treatment of a streptococcalinfection include but are not limited to penicillin or a derivativethereof or clindamycin, cephalosporins, glycopeptides (e.g.,vancomycin), and cycloserine.

The amount of active agent in a composition varies, however, dependingupon the health and physical condition of the individual to be treated,age, the taxonomic group of individual to be treated (e.g., non-humanprimate, primate, etc.), the capacity of the individual's immune systemto synthesize antibodies, the degree of protection desired, theformulation of the vaccine, the treating doctor's assessment of themedical situation, and other relevant factors. The amount will fall in arelatively broad range which can be determined through routine trials.

Kits

The invention also provides kits comprising one or more containers ofcompositions of the invention. Compositions can be in liquid form or canbe lyophilized, as can individual antigens. Suitable containers for thecompositions include, for example, bottles, vials, syringes, and testtubes. Containers can be formed from a variety of materials, includingglass or plastic. A container may have a sterile access port (forexample, the container may be an intravenous solution bag or a vialhaving a stopper pierceable by a hypodermic injection needle).

The kit can further comprise a second container comprising apharmaceutically-acceptable buffer, such as phosphate-buffered saline,Ringer's solution, or dextrose solution. It can also contain othermaterials useful to the end-user, including other buffers, diluents,filters, needles, and syringes. The kit can also comprise a second orthird container with another active agent, for example an antibiotic.

The kit can also comprise a package insert containing writteninstructions for methods of inducing immunity against streptoccalbacteria or for treating gram positive bacterial (e.g., streptococcaland/or staphylococcal) infections. The package insert can be anunapproved draft package insert or can be a package insert approved bythe Food and Drug Administration (FDA) or other regulatory body.

All patents, patent applications, and references cited in thisdisclosure are expressly incorporated herein by reference. The abovedisclosure generally describes the present invention. A more completeunderstanding can be obtained by reference to the following specificexamples, which are provided for purposes of illustration only and arenot intended to limit the scope of the invention.

Example 1 Immunogenicity of a Cna_B Domain

The Cna_B domain of GAS protein Cpa_M18 was cloned together with aflanking domain (Fb-signal) in a PET21b vector. See FIGS. 1A-B.His-tagged recombinant protein was purified using activated chelatingsepharose fast flow columns. See FIG. 2.

Antiserum against the cloned Cna_B-Fb domain was obtained by immunizing10 CD1 female mice three times each with 20 μg of the recombinantCna_B-Fb protein. Cna_B-Fb serum was then probed by western blotexperiments against a variety of purified His-tagged recombinantproteins from different human pathogens containing a Cna_B domain. Theresults are shown in FIGS. 3A-D. These experiments demonstrate that theCna_B domain is immunogenic and that antiserum raised against itrecognizes GAS_Cpa and F2 proteins as well as pili components of S.agalactiae and S. pneumoniae, which have been reported to be protectiveantigens (Maione et al., 2005 Science 309, 148-150; Rosini et al., 2006Mol. Micro. 61, 126-141 and Gianfaldoni et al., 2007, Infect. Immun. 75,1059-1062). Example 5 reports experiments designed to address thepossibility that antibodies in the sera reacted with the His tag; seealso FIG. 20.

Reactivity of the Cna_B antiserum was compared to that of antiserumspecific for the cpa_M18 protein using western blots. The results areshown in FIGS. 4A-B. Higher reactivity with all proteins tested wasobserved for the Cna_B antiserum. In particular, all the variants ofGBS_(—)59 (SAL 1486) tested were detected by the anti-Cna_B-Fb serum,but only one variant was detected by the anti-Cpa_M18 serum.

Example 2 Opsonophagocytosis Assays

Opsonophagocytic killing of S. agalactiae (GBS) using specific sera anddifferentiated HL-60 cells was investigated in vitro to test whether therecombinant Cna_B-Fb domain elicited protective antibodies. GBS weregrown in 5 ml of Todd Hewitt Broth (THB) to the mid exponential phase(OD₆₀₀=0.3), then centrifuged at 3000×g for 10 min at 4° C., washed withPBS lx, suspended, and diluted in OP buffer (HBSS, 0.1% gelatin, 10%fetal calf serum) to a final concentration of approximately 2×10⁷CFU/ml). GBS cells (approximately 2×10⁵ CFU) were mixed withheat-inactivated mouse serum (final concentration in the reaction 1:10)on wells of a chilled 96-well microtiter plate, then differentiated HL60(1−2×10⁶ cells) and baby rabbit complement were added on ice with GBScells (final reaction volume 125 μl). The mixtures were incubated for 60min at 37° C. and mixed at 400-500×g. Phagocytosis was ended byreturning the samples to ice at the end of the incubation period.Immediately before (time 0) and after 1 h incubation (time 1 h), a 25 μAaliquot was diluted in sterile distilled water (25 μl sample+225 μlwater, then 1:10 and 1:100) and plated in Tryptic soy agar plates with5% sheep blood. The plates were incubated overnight at 37° C.

The results are shown in FIG. 5. GAS_M18_Cna_B_Fb serum mediates thekilling of GBS strain 515 (which expresses the Cna_B domain in pilinproteins SAL 1482, SAL 1486 and SAL 1487) and of strain JM10098 (whichexpressed the protective pilins SAN 1518 and SAN 1519).

-   Further opsonophagocytosis experiments pointed out that GAS_M18_cpa    (the entire protein containing Cna_B-Fb domain) was equally able to    kill bacteria, suggesting that antibodies raised against Cna_B-Fb    domain are indeed responsible for bacterial killing.

In the absence of a suitable opsonophagocytosis system for S. pyogenes(GAS), R13, a mutant strain of GBS which lacks pili, and the same GBSR13 strain complemented with GAS pilus M1 and GAS pilus M6, were testedin opsonophagocytosis experiments. The results are shown in FIG. 6.These experiments demonstrate that GAS_M18_Cna_B_Fb antiserum mediatesthe killing of the GBS R13 strain which expresses GAS pili M1 and, to alesser extent, the killing of the GBS R13 strain which expresses piliM6.

Because the Fb-signal domain is present only in GAS Cpa proteins, butnot in the GBS pilins for which antibody-mediated killing wasdemonstrated, we focused on the Cna_B domain, which is present in allthe proteins tested in Example 1. The amino acid sequences of theseproteins were aligned to compare amino acid sequences of their Cna_Bdomains (FIGS. 7-13). These alignments identified a conserved region,termed herein the “G box,” which has the consensus sequenceGXYXLXEGXXXXXGY (SEQ ID NO:74).

Example 3 Survival of Cna_B-Fb Immunized Mice after GBS Challenge

Thirty CD1 female mice were immunized on days 1, 20, and 34 with therecombinant Cna_B-Fb domain of the S. pyogenes Spy_M18_(—)0126 proteinprepared as described in Example 1. Ten mice were IP injected with 20 μgof the recombinant protein in 100 μl of _PBS+100 μl Freund's incompleteadjuvant. As positive controls, five mice were injected with 20 μg of S.agalactiae GBS59 (SAL_(—)1486 protein in 100 μl of PBS+100 μl Freund'sincomplete adjuvant, and five mice were injected with 20 μg of S.agalactiae GBS1523 (SAN 1518) protein in 100 μl of PBS+100 μl Freund'sincomplete adjuvant. As negative controls, ten mice were injected withPBS plus Freund's incomplete adjuvant.

Mice were mated after the third injection, and newborns were challengedwith a lethal dose of either GBS strain A909 or GBS strain 515. Eightynewborns from mothers immunized with the Cna_B-Fb and 80 with PBS, andforty newborns each from mothers immunized with S. agalactiae GBS59(SAL_(—)1486) or S. agalactiae GBS1523 (SAN 1518) were challenged.Newborn survival was monitored for four days. The survival rate fornewborns immunized with the Cna_B-Fb domain was 42% and 44% afterchallenge with strains A909 and 515, respectively. The results are shownin Table 38, below.

TABLE 38 challenge strain injection with A909 515 Cna_B-Fb 42% 44% PBS(negative) control 15% 12% GBS1523 (SAN1518) (positive control) 79% ndGBS59 (SAL1486) (positive control) nd 86%

Results of a similar experiment are shown in FIG. 24.

Example 4 ELISA Assays

Evaluation of specific anti-Cna_B domain antibodies in GAS_Cpa_M18 serumwas performed by coating both GAS_Cpa_M18 protein and Cna_B domain,which were successively challenged by serial dilutions of GAS_Cpa_M18serum in an ELISA experiment (Tables 39 and 40). Dilutions correspondingto OD₅₄₀=1 indicated the ELISA titer for each protein (Table 40). FIG.19 shows that when Y=1 (OD₅₄₀) for GAS_Cpa_M18 ELISA titer was 627.814.Similarly, when Y=1 (OD₅₄₀) for GAS_Cpa_M18 when challenging the coatedCna_B domain the ELISA titer resulted 318.061. This experiment showedthat about half of the antibodies contained in GAS_Cpa_M18 protein serumwere specific for the Cna_B domain.

TABLE 39 Cpa_M18_serum Cpa_M18 full Coated protein length protein Cna_Bdomain ELISA titer 627.814 318.061

TABLE 40 serum dilution OD₅₄₀ nm anti_cpa_M18_std OD₄₅₀ nm anti_cna_B10000 3.407 3.136 20000 3.408 3.082 40000 3.282 2.553 80000 3.011 1.83160000 2.576 1.305 320000 1.425 0.769 640000 0.815 0.508 1280000 0.5050.295

Example 5 FACS Analysis of Cross-Reactivity of GAS Cna_B_Fb Domain Serumwith GAS and GBS strains

This example demonstrates that GAS Cna_B_Fb domain antiserumcross-reacts with strains of both GAS and GBS.

Antiserum against the cloned Cna_B-Fb domain and against the Cna_Bdomain only (“Cna_B_M6”; SEQ ID NO:145) was obtained by immunizing CD1female mice three times each with 20 μg of the recombinant Cna_B-Fbprotein or 20 μg of the recombinant M6_Cna_B domain.

Cross-hybridization specificity against various strains of GAS and GBSwas confirmed using Fluorescence Activated Cell Sorting (FACS). Athreshold of 80 channels was designated as a positive shift; 150channels was designated as a very positive shift.

The results are shown in Table 41. See also FIG. 18.

TABLE 41 MFI (Mean Fluorescence Intensity) Strains Sera M1Wessels M3_44M3_43 M6_16 27_M6 28_M6 CJB111_GBS 515_GBS JM_GBS 2177_GBS CD_11GBSα-CnaB_M18 220** 96* 64 \ \ \ 115*  94*  45  112* 228** α-CnaB_M6 \ \ \362** 100* 382** \ \ \ \ \ α-AP-1_M6 \ \ \ 520  390  300  \ \ \ \ \α-GBS_59 \ \ \ \ \ \ 458  421 \ \ 480  α-GBS_67 \ \ \ \ \ \ \ 725 \ \ \α-GBS_80 \ \ \ \ \ \ \ \ 487 367 \ α-GBS_1523 \ \ \ \ \ \ \ \ 506 517 \*>80 **>150

Example 6 In Vivo Protection from Subcutaneous Infection afterIntraperitoneal Immunization

This example demonstrates that mice immunized intraperitoneally withvarious Cna_B domain antigens show a reduced skin lesion area in a GASsubcutaneous infection model.

Mice were immunized intraperitoneally with 20 μg of Cna_B-Fb_M18 domainthree times on days 1, 21 and 35 and challenged two weeks after thethird immunization by subcutaneous injection of 10⁹ cfu of S. pyogenesstrain SF370_M1. Lesion areas were measured by evaluating the number ofpixels in pictures of the lesions using the QUANTITY ONE® method(Bio-Rad). Phosphate buffered saline (PBS) was used as a negativecontrol, and M1 protein (“emm-1”) was used as a positive control.Results from immunizations with the GAS Cna_B domain antigen“Cna_B-Fb_M18” are shown in FIGS. 21 and 25. Results from immunizationswith a GBS chimeric Cna_B domain antigen are shown in FIG. 25. Thechimeric GBS Cna_B domain antigen was “GBS_(—)59(515)-linker-GBS_(—)67”(SEQ ID NO:129), which is described in Example 8.

Example 7 In Vivo Protection from S. Aureus Challenge afterIntraperitoneal Immunization

This example demonstrates that intraperitoneal immunization with a Cna_Bdomain antigen protects against S. aureus colonization in a mouse renalabscess model

Mice (10 mice for each experiment) were immunized with a Cna_B domainantigen (Cna_B-Fb_M18; 20 μg/mouse) or with various S. aureus antigenswith the following schedule: at day 0 first immunization and at day 14second immunization. Challenge was performed at day 24. Immunizationswere done intraperitoneally. Immunized animals were challenged on day 24by intravenous injection of a bacterial suspension of S. aureus Newmanstrain. Cultures of Newman strain were centrifuged, washed twice, anddiluted in PBS before challenge. On day 28, mice were euthanized.Kidneys were removed and homogenized in 1% TRITON® X-100, aliquotsdiluted and plated on agar media for triplicate determination of CFU.PBS was used as a negative control. The results are shown in FIG. 22(“Cna_B” is Cna_B-Fb_M18).

Example 8 Cloning and Expression of Chimeric Cna_B Domain Antigens

The following chimeric Cna_B domain antigens were cloned and expressedin a pET15 expression vector using GBS59-Cna_B as first domain due toits high degree of solubility.

SEQ ID NO:127, shown below, is the amino acid sequence of a His-taggedCna_B domain antigen (“GBS_(—)59(515)-linker-GBS_(—)80”; SEQ ID NO:140)containing the Cna_B domain of SAL 1486 (“GBS59”) from GBS strain 515, alinker sequence, and the Cna_B domain of SAG 0645 (“GBS80”) from GBSstrain 2603V/R. The six histidine residues upstream from the chimericsequence are bolded. The amino acid linker sequence is bolded. Theunderlined amino acids were added to encourage protein folding.

HHHHHHLAGATFLVKKDGKYLARKSGVATDAEKAAVDSTKSALDAAVKAYNDLTKEKQEGQDGKSALATVSEKQKAYNDAFVKANYSYEWVEDKNAKNVVKLISNDKGQFEITGLTEGQYSLEETQAPTGYAKLSGDVSFNVNATSYSKGSAQDIE GSGGGGLGGAEFDLLASDGTAVKWTDALIKANTNKNYIAGEAVTGQPIKLKSHTDGTFEIKGLAYAVDANAEGTAVTYKLKETKAPEGYVIPDKEIEFTVSQTSYNTKPTDITVDS

SEQ ID NO:128, shown below, is the amino acid sequence of a His-taggedCna_B domain antigen (“GBS_(—)59(515)-linker-GBS_(—)1523”; SEQ IDNO:141) containing the Cna_B domain of SAL 1486 (“GBS59”) from GBSstrain 515, a linker sequence, and the Cna_B domain of SAN 1518(“GBS1523”) from GBS strain COH1. The six histidine residues upstreamfrom the chimeric sequence are bolded. The amino acid linker sequence isbolded. The underlined amino acids were added to encourage proteinfolding.

HHHHHHLAGATFLVKKDGKYLARKSGVATDAEKAAVDSTKSALDAAVKAYNDLTKEKQEGQDGKSALATVSEKQKAYNDAFVKANYSYEWVEDKNAKNVVKLISNDKGQFEITGLTEGQYSLEETQAPTGYAKLSGDVSFNVNATSYSKGSAQDIE GSGGGGLQGAIFVLKNATGQFLNFNDTNNVEWGTEANATEYTTGADGIITITGLKEGTYYLVEKKAPLGYNLLDNSQKVILGDG ATDTTNSD

SEQ ID NO:129, shown below, is the amino acid sequence of a His-taggedCna_B domain antigen (“GBS_(—)59(515)-linker-GBS_(—)67”; SEQ ID NO:142)containing the Cna_B domain of SAL 1486 (“GBS59”) from GBS strain 515, alinker sequence, and the two Cna_B domains of SAL 1487 (“GBS67”) fromGBS strain 515 (the second domain is italicized). The six histidineresidues upstream from the chimeric sequence are bolded. The amino acidlinker sequence is bolded. The underlined amino acids were added toencourage protein folding.

HHHHHHLAGATFLVKKDGKYLARKSGVATDAEKAAVDSTKSALDAAVKAYNDLTKEKQEGQDGKSALATVSEKQKAYNDAFVKANYSYEWVEDKNAKNVVKLISNDKGQFEITGLTEGQYSLEETQAPTGYAKLSGDVSFNVNATSYSKGSAQDIE GSGGGGLSKATFVLKTTAHPESKIEKVTAELTGEATFDNLIPGDYTLSEETAPEGYKKTNQTWQVKVESNGKTTIQNSG LKGATFELQEFNEDYKLYLPIKNNNSKVVTGENGKISYKDLKDGKYQLIEAVSPEDYQKITNKPILTFEVVKGSIKNIIAVN KQI

SEQ ID NO:130, shown below, is the amino acid sequence of a His-taggedCna_B domain antigen(“GBS_(—)59(515)-GBS_(—)80-linker-GBS_(—)1523-linker”; SEQ ID NO:143)containing the Cna_B domain of SAL 1486 (“GBS59”) from GBS strain 515,the Cna_B domain of SAG 0645 from GBS strain 2603V/R, a linker sequence,the Cna_B domain of SAN 1518 from GBS strain COH1, and another linkersequence. The six histidine residues upstream from the chimeric sequenceare bolded. The amino acid linker sequence is bolded. The underlinedamino acids were added to encourage protein folding.

HHHHHHLAGATFLVKKDGKYLARKSGVATDAEKAAVDSTKSALDAAVKAYNDLTKEKQEGQDGKSALATVSEKQKAYNDAFVKANYSYEWVEDKNAKNVVKLISNDKGQFEITGLTEGQYSLEETQAPTGYAKLSGDVSFNVNATSYSKGSAQDIELGGAEFDLLASDGTAVKWTDALIKANTNKNYIAGEAVTGQPIKLKSHTDGTFEIKGLAYAVDANAEGTAVTYKLKETKAPEGYVIPDKEIEFTVSQTSYNTKPTDITVDS GSGGGGLQGAIFVLKNATGQFLNFNDTNNVEWGTEANATEYTTGADGIITITGLKEGTYYLVEKKAPLGYNLLDNSQKVILGDGATDTTNSDGS GGGG

SEQ ID NO:131, shown below, is the amino acid sequence of a His-taggedCna_B domain antigen (“SA Cna_B-SdrD”; SEQ ID NO:144) containing Cna_Bdomains of S. aureus SdrD protein and including “linker” amino acids(bolded) which occur naturally in the SdrD protein. The six histidineresidues upstream from the chimeric sequence are bolded.

HHHHHHVGNVTVTVFDNNTNTKVGEAVTKEDGSYLIPNLPNGDYRVEFSNLPKGYEVTPSKQGNNEELDSNGLSSVITVNGKDNLSADLGIYKPKYNLGDYVWEDTNKNGIQDQDEKGISGVTVTLKDENGNVLKTVTTDADGKYKFTDLDNGNYKVEFTTPEGYTPTTVTSGSDIEKDSNGLTTTGVINGADNMTLDSGFYKTPKYNLGNYVWEDTNKDGKQDSTEKGISGVTVTLKNENGEVLQTTKTDKDGKYQFTGLENGTYKVEFETPSGYTPTQVGSGTDEGIDSNGTSTTGVIKDKDNDTIDSGFYKPTYNLGDYVWEDTNKNGVQDKDEKGISGVTVTLKDENDKVLKTVTTDENGKYQFTDLNNGTYKVEFETPSGYTPTSVTSGNDTEKDSNGLTTTGVIKDADNMTLDSGFYKTPKYSLGDYVWYDSNKDGKQDSTEKGIKDVKVTLLNEKGEVIGTTKTDENGKYCFDNLDSGKYKVIFEKPAGLTQTVTNTTEDDKDADGGEVDVTIT

Example 9 Intraperitoneal Immunization with a Cna_B Domain AntigenProtects Against S. Aureus Colonization in a Mouse Renal Abscess Model

This example demonstrates that intraperitoneal immunization with a Cna_Bdomain antigen protects against S. aureus colonization in a mouse renalabscess model.

Mice (10 mice for each experiment) were immunized with a Cna_B domainantigen (Cna_B-Fb_M18; 20 μg/mouse) with the following schedule: at day0 first immunization and at day 14 second immunization. Challenge wasperformed at day 24. Immunizations were done intraperitoneally.Immunized animals were challenged on day 24 by intravenous injection ofa bacterial suspension of S. aureus Newman strain. Cultures of Newmanstrain were centrifuged, washed twice, and diluted in PBS beforechallenge. On day 28, mice were euthanized. Kidneys were removed andhomogenized in 1% TRITON® X-100, aliquots diluted and plated on agarmedia for triplicate determination of CFU. The Staphylococcus proteinIsdB was used as a positive control, and alum was the negative control.Mice immunized with the Cna_B domain antigen showed reduced renalcolonization rate after S. aureus challenge. The results are shown inFIG. 23.

Example 10 Cna_B_SdrD Confers Protection in a Sepsis Mouse Model AgainstS. Aureus Infection

This example demonstrates that a Cna_B domain antigen (FIG. 27; SEQ IDNO:132) comprising Cna_B domains (SEQ ID NOS:134-138) of the S. aureusprotein SdrD (FIGS. 26A, B) confers protection in a sepsis mouse modelagainst S. aureus infection.

Groups of 14 mice each were immunized with the Cna_B_SdrD antigen (20μg/mouse in alum) or a mutant form of S. aureus α-hemolysin (20 μg/mousein alum) which cannot form pores (H1a_(H35L); see, e.g., Wardenburg &Schneewind, “Vaccine protection against Staphlococcus aureus pneumonia,”Exp Med. 2008 Feb. 18; 205(2): 287-294). Control mice were injected withalum.

Mice were immunized with the following schedule: at day 0 firstimmunization and at day 14 second immunization. Challenge was performedat day 24. Immunizations were done intraperitoneally. Immunized animalswere challenged on day 24 by intraperitoneal injection of a bacterialsuspension of S. aureus strain USA300. Cultures of USA300 strain werecentrifuged, washed twice and diluted in PBS before challenge. Mice weredaily monitored for 14 days and euthanized at the appearance of humaneendpoints, in agreement with Novartis Animal Welfare Policies. Thepercent survival two weeks after challenge with S. aureus strain USA300is shown in FIG. 28. These results demonstrate that immunization withCna_B_SdrD confers an high protection against S. aureus challengesuggesting this domain as a potential very good vaccine candidate.

TABLE 42 Sequence identifiers SEQ ID sequence of NO: FIG. Cpa_M18 Cna_Band Fb 1  1 Cna_B_CPA_M5_MANFREDO 2  7 (Spy_M5_0104) Cna_B_CPA_M28(M28_Spy0107) 3  7 Cna_B_CPA_M12 (MGAS2096_Spy0113) 4  7 Cna_B_CPA_M1(M5005_Spy_0107) 5  7 Cna_B_CPA_M3 (SpyM3_0098) 6  7 Cna_B_CPA_M18(Spy_M18_0126) 7 7, 9, 10, 11, 12, 13, 16, 17 Cna_B_CPA_M6 (M6_Spy0159)8  7 Cna_B_CPA_M4_C (MGAS10750_Spy0115) 9  7 Cna_B_CPA_M28(MGAS10270_Spy0113) 10  7 G box 11  7 G box 12  7 G box 13  7 G box 147, 14, 15 G box 15  7 G box 16  7 G box 17  7 Spy_M5_0104 18 —M28_Spy0107 19 — MGAS2096_Spy0113 20 — M5005_Spy_0107 21 — SpyM3_0098 22— Spy_M18_0126 23 — M6_Spy0159 24 — MGAS10750_Spy0115 25 —MGAS10270_Spy0113 26 — Cna_B_GBS_52 (SAG_0646) 27 8, 9 Cna_B_GBS_150(SAL 1482) 28 8, 10 Cna_B_GBS_104_1 (SAG 0649) 29 8, 9 Cna_B_GBS_67 (SAL1487) 30 8, 10 Cna_B_GBS_1523 (SAN 1518) 31 8, 11 Cna_B_GBS_1524 (SAN1519) 32 8, 11 Cna_B_GBS_80 (SAG 0645) 33 8, 9 Cna_B_GBS_104_2 (SAG0649) 34 8, 9 Cna_B_GBS_1521 (SAN 1516) 35  8 G box 36  8 G box 37  8 Gbox 38  8 G box 39  8 G box 40  8 G box 41  8 G box 42  8 G box 43  8 Gbox 44  8 SAG_0646 45 — SAL 1482 46 — SAG 0649 47 — SAL 1487 48 — SAN1518 49 — SAN 1519 50 — SAG 0645 51 — SAN 1516 52 — Cna_B domain RRGB(SP_0463) 53 12 Cna_B domain RRGA1 (SP_0462) 54 12 Cna_B domain RRGC2(SP_0464) 55 12 Cna_B domain RRGA2 (SP_0462) 56 12 Cna_B domain RRGC1(SP_0464) 57 12 G box 58 12 G box 59 12 G box 60 12 G box 61 12 G box 6212 SP_0463 63 — SP_0462 64 — SP_0464 65 — Cna_B domain Ser-Asp rich2(SdrD 66 13 MW0517) Cna_B domain Ser-Asp rich3 (SdrD 67 13 MW0517) Cna_Bdomain CBP (MW2612) 68 13 G box 69 13 G box 70 13 G box 71 13 SdrDMW0517 72 — MW2612 73 — G box consensus sequence 74 — Cna_B_Bkb3 (DUF11) 89/1591 75 14 Cna_B_Bkb1 SSU05_0474 05ZYH33 76 14 BKB SEQ0936 77 15G box 78 15 linker 79 — Cna_B_autotransporter 80 16(SSU05_0474[Streptococcus suis 05ZYH33] Cna_B (Protein of unknownfunction 81 16 DUF11: Surface protein from Gram- positive cocci, anchorregion [Streptococcus suis 89/1591] SSU05_0474[Streptococcus suis 82 —05ZYH33 Protein of unknown function 83 — DUF11: Surface protein fromGram- positive cocci, anchor region [Streptococcus suis 89/1591Cna_B_ap1 (SEQ0935*) 84 17 Cna_B_ap2 (SEQ0935*) 85 17 Cna_B_bkb(SEQ0936**) 86 17 * SEQ0935 ancillary protein 87 — SEQ0935 undefinedproduct 914186:916159 forward MW: 73872 67 ** SEQ0936 BKB SEQ0936undefined 88 — product 916183:917625 forward MW: 51902 46.3 S. suisstrain 05ZYH33 89 — S. suis strain 05ZYH33 90 — S. suis strain 05ZYH3391 — S. suis strain 05ZYH33 92 — S. suis strain 98HAH33 93 — S. suisstrain 98HAH33 94 — S. suis strain 98HAH33 95 — Streptococcus suis89/1591 96 — S. suis strain 05ZYH33 97 — S. equi FszE: Sez_1828 98 — S.equi FszD: Sez_1822 99 — S. equi FszC: Sez_1821 100 — S. equi FbpZ:Sez_1825 101 — GBS59 (SAL 1486) 102 — SAL 1486 Cna_B 103 13 SAL 1486 GBox 104 13 Cpa_M6 S. pyogenes vWFA 105 — (M6_Spy0159) SAL_1487 cell wallsurface anchor 106 — family protein vWFA Ancillary pilus subunit S.pneumoniae 107 — vWFA RrgA (SP_0462) multi-Cna_B domain antigen 108 —multi-Cna_B domain antigen 109 — Cna_B domain of SAL_1487 110 — Cna_Bdomain of SAL_1487 111 — Cna_B domain of SAG 0645 112 — Cna_B domain ofSAL_1518 113 — Cna_B domain of SAL_1486 114 — Cna_B domain of SAL_1486115 — Cna_B domain of SAG_1407 116 — Cna_B domain of SAG_1407 117 —SAG_1407 118 — nucleotide sequence encoding GAS 119 — protein F2 Spy0119Cna_B_M6 Spy_0159 120 — GAS protein F2 Spy0119 121 — Cna_B domain 1 ofNO: 121 122 — Cna_B domain 2 of NO: 121 123 — Cna_B domain 3 of NO: 121124 — Cna_B domain 4 of NO: 121 125 — Cna_B domain 5 of NO: 121 126 —His-tagged GBS_59(515)-linker- 127 — GBS_80 His-taggedGBS_59(515)-linker- 128 — GBS_1523 His-tagged GBS_59(515)- 129 —linker_GBS_67 His-tagged GBS_59(515)-GBS_80- 130 —linker-GBS_1523-linker His-tagged SA Cna_B-SdrD 131 — SA SdrD protein132 27 Cna_B_SdrD antigen (Example 10) 133 28 Cna_B domain of SdrD 134 27B Cna_B domain of SdrD 135  27B Cna_B domain of SdrD 136  27B Cna_Bdomain of SdrD 137  27B Cna_B domain of SdrD 138  27B Cna_B_SdrD antigen(Example 10) 139 28 GBS_59(515)-linker-GBS_80 140 —GBS_59(515)-linker-GBS_1523 141 — GBS_59(515)-linker_GBS_67 142 —GBS_59(515)-GBS_80-linker- 143 — GBS_1523-linker SA Cna_B-SdrD 144 —Cna_B_M6 145 —

1. A nucleic acid molecule which encodes: (1) a Cna_B domain antigenselected from the group consisting of: (a) a Cna_B domain antigencomprising the amino acid sequence SEQ ID NO:5, wherein amino acid 1 ofSEQ ID NO:5 is not linked by a peptide bond to-amino acid 311 of SEQ IDNO:21 and/or amino acid 70 of SEQ ID NO:5 is not linked by a peptidebond to amino acid 382 of SEQ ID NO:21; (b) a Cna_B domain antigen whichconsists of the amino acid sequence SEQ ID NO:5 and 307, 308, 309, or310 additional contiguous amino acids of SEQ ID NO:21 at the N terminusof SEQ ID NO:5; (c) a Cna_B domain antigen which consists of the aminoacid sequence SEQ ID NO:5 and 307, 308, 309, or 310 additionalcontiguous amino acids of SEQ ID NO:21 at the N terminus of SEQ ID NO:5and 0-380 additional contiguous amino acids of SEQ ID NO:21 at the Cterminus of SEQ ID NO:5; and (d) a Cna_B domain antigen which consistsof the amino acid sequence SEQ ID NO:5, and wherein the Cna_B domainantigen is not a native gram positive bacterial protein; or (2) a fusionpolypeptide comprising the Cna_B domain antigen.
 2. The nucleic acidmolecule of claim 2, which is an expression vector.
 3. A host cellcomprising an expression vector, wherein the expression vector encodes:(1) a Cna_B antigen selected from the group consisting of: (a) a Cna_Bdomain antigen comprising the amino acid sequence SEQ ID NO:5, whereinamino acid 1 of SEQ ID NO:5 is not linked by a peptide bond to-aminoacid 311 of SEQ ID NO:21 and/or amino acid 70 of SEQ ID NO:5 is notlinked by a peptide bond to amino acid 382 of SEQ ID NO:21; (b) a Cna_Bdomain antigen which consists of the amino acid sequence SEQ ID NO:5 and307, 308, 309, or 310 additional contiguous amino acids of SEQ ID NO:21at the N terminus of SEQ ID NO:5; (c) a Cna_B domain antigen whichconsists of the amino acid sequence SEQ ID NO:5 and 307, 308, 309, or310 additional contiguous amino acids of SEQ ID NO:21 at the N terminusof SEQ ID NO:5 and 0-380 additional contiguous amino acids of SEQ IDNO:21 at the C terminus of SEQ ID NO:5; and; (d) a Cna_B domain antigenwhich consists of the amino acid sequence SEQ ID NO:5, and wherein theCna_B domain antigen is not a native gram positive bacterial protein; or(2) a fusion polypeptide comprising the Cna_B antigen.
 4. A method ofproducing a polypeptide, comprising: culturing the host cell of claim 3under conditions under which the expression vector expresses thepolypeptide; and recovering the polypeptide.
 5. An isolated antibodywhich binds selectively to one or more Cna_B domains, wherein each Cna_Bdomain comprises an amino acid sequence selected from the groupconsisting of SEQ ID NOS:1-10, 27-35, 53-57, 66-68, 74-76, 80, 81,84-86, 110-117, 122-126, and 134-144.
 6. The antibody of claim 5 whichbinds to a polypeptide comprising the amino acid sequence SEQ ID NO:1.7. The antibody of claim 5 which is a monoclonal antibody.
 8. Theantibody of claim 5 which induces opsonophagocytosis of GBS strain 515by at least 30%.